Skip to main content

Advertisement

SpringerLink
Log in

Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa

  • Human Genetics • Review
  • Published:
Journal of Applied Genetics Aims and scope Submit manuscript

Abstract

Epidermolysis bullosa (EB) is a group of rare genetic skin fragility disorders, which are hereditary. These disorders are associated with mutations in at least 16 genes that encode components of the epidermal adhesion complex. Currently, there are no effective treatments for this disorder. All current treatment approaches focus on topical treatments to prevent complications and infections. In recent years, significant progress has been achieved in the treatment of the severe genetic skin blistering condition known as EB through preclinical and clinical advancements. Promising developments have emerged in the areas of protein and cell therapies, such as allogeneic stem cell transplantation; in addition, RNA-based therapies and gene therapy approaches have also become a reality. Stem cells obtained from embryonic or adult tissues, including the skin, are undifferentiated cells with the ability to generate, maintain, and replace fully developed cells and tissues. Recent advancements in preclinical and clinical research have significantly enhanced stem cell therapy, presenting a promising treatment option for various diseases that are not effectively addressed by current medical treatments. Different types of stem cells such as primarily hematopoietic and mesenchymal, obtained from the patient or from a donor, have been utilized to treat severe forms of diseases, each with some beneficial effects. In addition, extensive research has shown that gene transfer methods targeting allogeneic and autologous epidermal stem cells to replace or correct the defective gene are promising. These methods can regenerate and restore the adhesion of primary keratinocytes in EB patients. The long-term treatment of skin lesions in a small number of patients has shown promising results through the transplantation of skin grafts produced from gene-corrected autologous epidermal stem cells. This article attempts to summarize the current situation, potential development prospects, and some of the challenges related to the cell therapy approach for EB treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

EB:

Epidermolysis bullosa

TEM:

Transmission electron microscopy

ACT:

Autologous cell therapy

DEB:

Dystrophic EB

JEB:

Junctional EB

EBS:

EB simplex

KEB:

Kindler EB

AR:

Autosomal recessive

RDEB:

Recessive dystrophic epidermolysis bullosa

DDEB:

Dominant dystrophic epidermolysis bullosa

NEBR:

National Epidermolysis Bullosa Registry

ECM:

Extracellular matrix

HMGB1:

High mobility group box 1

PDGF:

Platelet-derived growth factor

T4:

Thymosin 4

iPSCs:

Induced pluripotent stem cells

MSCs:

Mesenchymal stem/stromal cells

BMT:

Bone marrow transplantation

BMZ:

Basement membrane zone

BMMSCs:

Bone marrow mesenchymal stem cells

BM:

Bone marrow

LAM5:

Laminin 5

DSB:

Double-strand break

NHEJ:

Non-homologous end joining

HDR:

Homology-directed repair

AAVS1:

Adeno-associated virus integration site 1

ZFN:

Zinc-finger nuclease

EpSCs:

Epithelial stem cells

IDLVs:

Integration-defective lentiviral vectors

TALE:

Transcription activator-like effector

gRNA:

Guide RNA

KRT14:

Keratin 14

TALENs:

Transcription activator-like effector nucleases

COL7A1:

Collagen type VII alpha 1 chain

KLHL24:

Kelch-like family member 24

BPAG:

Bullous pemphigoid antigen

PLEC1:

Plectin1

HSV:

Herpes simplex virus

CRISPR:

Clustered regularly interspaced palindromic repeats

SMaRT:

Spliceosome-mediated RNA trans-splicing

References

  • Aikawa E et al (2015) Systemic high-mobility group box 1 administration suppresses skin inflammation by inducing an accumulation of PDGFRα+ mesenchymal cells from bone marrow. Sci Rep 5(1):1–13

    Article  Google Scholar 

  • Alexeev V, Uitto J, Igoucheva O (2011) Gene expression signatures of mouse bone marrow-derived mesenchymal stem cells in the cutaneous environment and therapeutic implications for blistering skin disorder. Cytotherapy 13(1):30–45

    Article  CAS  PubMed  Google Scholar 

  • Alvin G (2021) Cell therapy: the new approach to der-matology and dermatologic surgery. Clin Surg 5(8):1–14

    Google Scholar 

  • Angelova-Fischer I et al (2005) Kindler syndrome: a case report and proposal for clinical diagnostic criteria. Acta Dermatovenerol Alp Panonica Adriat 14:61–67

    Google Scholar 

  • Arabi F, Mansouri V, Ahmadbeigi N (2022) Gene therapy clinical trials, where do we go? An overview. Biomed Pharmacother 153:113324

    Article  CAS  PubMed  Google Scholar 

  • Arin MJ (2009) The molecular basis of human keratin disorders. Hum Genet 125(4):355–373

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  • Ashton G (2004) Kindler syndrome. Clin Exp Dermatol 29(2):116–121

    Article  CAS  PubMed  Google Scholar 

  • Ashton G et al (2001) α6β4 integrin abnormalities in junctional epidermolysis bullosa with pyloric atresia. Br J Dermatol 144(2):408–414

    Article  CAS  PubMed  Google Scholar 

  • Atkinson SD et al (2011) Development of allele-specific therapeutic siRNA for keratin 5 mutations in epidermolysis bullosa simplex. J Investig Dermatol 131(10):2079–2086

    Article  CAS  PubMed  Google Scholar 

  • Aumailley M et al (2005) A simplified laminin nomenclature. Matrix Biol 24(5):326–332

    Article  CAS  PubMed  Google Scholar 

  • Aushev M et al (2017) Traceless targeting and isolation of gene-edited immortalized keratinocytes from epidermolysis bullosa simplex patients. Mol Ther Methods Clin Dev 6:112–123

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Baardman R et al (2021) Novel insights into the epidemiology of epidermolysis bullosa (EB) from the Dutch EB Registry: EB more common than previously assumed? J Eur Acad Dermatol Venereol 35(4):995–1006

    Article  CAS  PubMed  Google Scholar 

  • Balistreri CR et al (2020) Stem cell therapy: old challenges and new solutions. Mol Biol Rep 47(4):3117–3131

    Article  CAS  PubMed  Google Scholar 

  • Bardhan A et al (2020) Epidermolysis bullosa. Nat Rev Dis Primers 6(1):1–27

    Article  Google Scholar 

  • Bartel RL (2015) Stem cells and cell therapy: autologous cell manufacturing. In: Translational regenerative medicine. Elsevier, pp 107–112

    Chapter  Google Scholar 

  • Bartoszewski R, Sikorski AF (2019) Editorial focus: understanding off-target effects as the key to successful RNAi therapy. Cell Mol Biol Lett 24(1):1–23

    Article  Google Scholar 

  • Bauer J et al (2017) Closure of a large chronic wound through transplantation of gene-corrected epidermal stem cells. J Invest Dermatol 137(3):778–781

    Article  CAS  PubMed  Google Scholar 

  • Baum C et al (2003) Side effects of retroviral gene transfer into hematopoietic stem cells. Blood, J Am Soc Hematol 101(6):2099–2113

    CAS  Google Scholar 

  • Benati D et al (2018) CRISPR/Cas9-mediated in situ correction of LAMB3 gene in keratinocytes derived from a junctional epidermolysis bullosa patient. Mol Ther 26(11):2592–2603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bennett CF, Swayze EE (2010) RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 50:259–293

    Article  CAS  PubMed  Google Scholar 

  • Bolling M et al (2011) Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients. Br J Dermatol 164(3):637–644

    CAS  PubMed  Google Scholar 

  • Bonaventura G et al (2021) Stem cells: innovative therapeutic options for neurodegenerative diseases? Cells 10(8):1992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bordet T, Behar-Cohen F (2019) Ocular gene therapies in clinical practice: viral vectors and nonviral alternatives. Drug Discov Today 24(8):1685–1693

    Article  CAS  PubMed  Google Scholar 

  • Bordignon C et al (1999) Cell therapy: achievements and perspectives. Haematologica 84(12):1110–1149

    CAS  PubMed  Google Scholar 

  • Bornert O et al (2016) Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy. Mol Ther 24(7):1302–1311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bornert O et al (2021) QR-313, an antisense oligonucleotide, shows therapeutic efficacy for treatment of dominant and recessive dystrophic epidermolysis bullosa: a preclinical study. J Investig Dermatol 141(4):883–893

    Article  CAS  PubMed  Google Scholar 

  • Bremer J et al (2016) Antisense oligonucleotide-mediated exon skipping as a systemic therapeutic approach for recessive dystrophic epidermolysis bullosa. Mol Ther Nucleic Acids:5

  • Bruckner AL et al (2020) The challenges of living with and managing epidermolysis bullosa: insights from patients and caregivers. Orphanet J Rare Dis 15(1):1–14

    Article  PubMed  PubMed Central  Google Scholar 

  • Bruckner-Tuderman L et al (2013) Progress in epidermolysis bullosa research: summary of DEBRA International Research Conference 2012. J Investig Dermatol 133(9):2121–2126

    Article  CAS  PubMed  Google Scholar 

  • Carter DM et al (1987) Treatment of junctional epidermolysis bullosa with epidermal autografts. J Am Acad Dermatol 17(2):246–250

    Article  CAS  PubMed  Google Scholar 

  • Chino T et al (2008) Bone marrow cell transfer into fetal circulation can ameliorate genetic skin diseases by providing fibroblasts to the skin and inducing immune tolerance. Am J Pathol 173(3):803–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Christiano AM et al (1994) Cloning of human type VII collagen. Complete primary sequence of the alpha 1 (VII) chain and identification of intragenic polymorphisms. J Biol Chem 269(32):20256–20262

    Article  CAS  PubMed  Google Scholar 

  • Cogan J et al (2014) Aminoglycosides restore full-length type VII collagen by overcoming premature termination codons: therapeutic implications for dystrophic epidermolysis bullosa. Mol Ther 22(10):1741–1752

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Coluccio A et al (2013) Targeted gene addition in human epithelial stem cells by zinc-finger nuclease-mediated homologous recombination. Mol Ther 21(9):1695–1704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Condrat I et al (2019) Junctional epidermolysis bullosa: allelic heterogeneity and mutation stratification for precision medicine. Front Med 5:363

    Article  Google Scholar 

  • Cong L et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121):819–823

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Conget P et al (2010) Replenishment of type VII collagen and re-epithelialization of chronically ulcerated skin after intradermal administration of allogeneic mesenchymal stromal cells in two patients with recessive dystrophic epidermolysis bullosa. Cytotherapy 12(3):429–431

    Article  CAS  PubMed  Google Scholar 

  • Coulombe PA, Kerns ML, Fuchs E (2009) Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility. J Clin Invest 119(7):1784–1793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cutlar L, Greiser U, Wang W (2014) Gene therapy: pursuing restoration of dermal adhesion in recessive dystrophic epidermolysis bullosa. Exp Dermatol 23(1):1–6

    Article  CAS  PubMed  Google Scholar 

  • Dang N, Murrell DF (2008) Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosa. Exp Dermatol 17(7):553–568

    Article  CAS  PubMed  Google Scholar 

  • Das BB, Sahoo S (2004) Dystrophic epidermolysis bullosa. J Perinatol 24(1):41–47

    Article  PubMed  Google Scholar 

  • Dasgeb B et al (2018) Colchicine: an ancient drug with novel applications. Br J Dermatol 178(2):350–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Luca M et al (2019) Advances in stem cell research and therapeutic development. Nat Cell Biol 21(7):801–811

    Article  PubMed  Google Scholar 

  • De Rosa L et al (2020) Toward combined cell and gene therapy for genodermatoses. Cold Spring Harb Perspect Biol 12(5):a035667

    Article  PubMed  PubMed Central  Google Scholar 

  • Dias N, Stein C (2002) Antisense oligonucleotides: basic concepts and mechanisms. Mol Cancer Ther 1(5):347–355

    CAS  PubMed  Google Scholar 

  • Dominici M et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    Article  CAS  PubMed  Google Scholar 

  • Eady R, Dopping-Hepenstal (2010) Transmission electron microscopy for the diagnosis of epidermolysis bullosa. Dermatol Clin 28(2):211–222

    Article  CAS  PubMed  Google Scholar 

  • Ebens C et al (2019) Bone marrow transplant with post-transplant cyclophosphamide for recessive dystrophic epidermolysis bullosa expands the related donor pool and permits tolerance of nonhaematopoietic cellular grafts. Br J Dermatol 181(6):1238–1246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eichstadt S et al (2019a) Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa. JCI insight 4(19)

  • Eichstadt S et al (2019b) Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa. JCI. Insight 4(19)

  • Eisenberg M et al (1987) Successful engraftment of cultured human epidermal allograft in a child with recessive dystrophic epidermolysis bullosa. Med J Aust 147(10):520–521

    Article  CAS  PubMed  Google Scholar 

  • Farokhforghani S et al (2021) Epidermolysis bullosa registry data in Iran. World J Plast Surg 10(3):99

    Article  PubMed  PubMed Central  Google Scholar 

  • Felts KA et al (2002) Functional cloning using pFB retroviral cDNA expression libraries. Mol Biotechnol 22(1):25–32

    Article  CAS  PubMed  Google Scholar 

  • Fine J-D (2010) Inherited epidermolysis bullosa. Orphanet J Rare Dis 5(1):1–17

    Article  Google Scholar 

  • Fine J-D (2016) Epidemiology of inherited epidermolysis bullosa based on incidence and prevalence estimates from the National Epidermolysis Bullosa Registry. JAMA Dermatol 152(11):1231–1238

    Article  PubMed  Google Scholar 

  • Fine J-D et al (1991) Revised clinical and laboratory criteria for subtypes of inherited epidermolysis bullosa: a consensus report by the subcommittee on diagnosis and classification of the National Epidermolysis Bullosa Registry. J Am Acad Dermatol 24(1):119–135

    Article  CAS  PubMed  Google Scholar 

  • Fine J-D et al (2008) The classification of inherited epidermolysis bullosa (EB): report of the third international consensus meeting on diagnosis and classification of EB. J Am Acad Dermatol 58(6):931–950

    Article  PubMed  Google Scholar 

  • Fine J-D et al (2014) Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 70(6):1103–1126

    Article  PubMed  Google Scholar 

  • Firing C, Bygum A (2017) Epidermolysis bullosa. Ugeskr Laeger 179(47)

  • Fontao L et al (2004) Molecular consequences of deletion of the cytoplasmic domain of bullous pemphigoid 180 in a patient with predominant features of epidermolysis bullosa simplex. J Investig Dermatol 122(1):65–72

    Article  CAS  PubMed  Google Scholar 

  • Foster L, Holmes Y (2007) Transition from paediatric to adult service in epidermolysis bullosa. Br J Nurs 16(4):244–246

    Article  PubMed  Google Scholar 

  • Fry LE et al (2020) RNA editing as a therapeutic approach for retinal gene therapy requiring long coding sequences. Int J Mol Sci 21(3):777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujita Y et al (2021) Intravenous allogeneic multilineage-differentiating stress-enduring cells in adults with dystrophic epidermolysis bullosa: a phase 1/2 open-label study. J Eur Acad Dermatol Venereol 35(8):e528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallico GG III et al (1984) Permanent coverage of large burn wounds with autologous cultured human epithelium. N Engl J Med 311(7):448–451

    Article  PubMed  Google Scholar 

  • Gear R et al (2022) Epidemiological, clinical, pathological and genetic characteristics of epidermolysis bullosa in New Zealand. Australas J Dermatol 63(1):62–67

    Article  PubMed  Google Scholar 

  • Goldschneider KR et al (2014) Pain care for patients with epidermolysis bullosa: best care practice guidelines. BMC Med 12(1):1–23

    Article  Google Scholar 

  • Gostyńska KB et al (2019) Allogeneic haematopoietic cell transplantation for epidermolysis bullosa: the Dutch experience. Acta Derm Venereol 99(3):347–348

    Article  PubMed  Google Scholar 

  • Goto M et al (2006) Targeted skipping of a single exon harboring a premature termination codon mutation: implications and potential for gene correction therapy for selective dystrophic epidermolysis bullosa patients. J Investig Dermatol 126(12):2614–2620

    Article  CAS  PubMed  Google Scholar 

  • Green H, Kehinde O, Thomas J (1979) Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Proc Natl Acad Sci 76(11):5665–5668

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Guleria I et al (2022) How do I: evaluate the safety and legitimacy of unproven cellular therapies? Transfusion 62(3):518–532

    Article  PubMed  Google Scholar 

  • Guo C et al (2023) Off-target effects in CRISPR/Cas9 gene editing. Front Bioeng Biotechnol 11:1143157

    Article  PubMed  PubMed Central  Google Scholar 

  • Gurevich I et al (2022) In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med 28(4):780–788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haniffa MA et al (2007) Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. J Immunol 179(3):1595–1604

    Article  CAS  PubMed  Google Scholar 

  • Haniffa MA et al (2009) Mesenchymal stem cells: the fibroblasts’ new clothes? Haematologica 94(2):258–263

    Article  CAS  PubMed  Google Scholar 

  • Has C (2017) The “Kelch” surprise: KLHL24, a new player in the pathogenesis of skin fragility. J Investig Dermatol 137(6):1211–1212

    Article  CAS  PubMed  Google Scholar 

  • Has C, South A, Uitto J (2020b) Molecular therapeutics in development for epidermolysis bullosa: update 2020. Mol Diagn Ther 24(3):299–309

    Article  PubMed  PubMed Central  Google Scholar 

  • Has C et al (2018) Epidermolysis bullosa: molecular pathology of connective tissue components in the cutaneous basement membrane zone. Matrix Biol 71:313–329

    Article  PubMed  Google Scholar 

  • Has C et al (2020a) Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol 183(4):614–627

    Article  CAS  PubMed  Google Scholar 

  • Hauschild-Quintern J et al (2013) Gene knockout and knockin by zinc-finger nucleases: current status and perspectives. Cell Mol Life Sci 70(16):2969–2983

    Article  CAS  PubMed  Google Scholar 

  • Heagerty A et al (1987) Rapid prenatal diagnosis of epidermolysis bullosa letalis using GB3 monoclonal antibody. Br J Dermatol 117(3):271–275

    Article  CAS  PubMed  Google Scholar 

  • Herz C et al (2006) Kindlin-1 is a phosphoprotein involved in regulation of polarity, proliferation, and motility of epidermal keratinocytes. J Biol Chem 281(47):36082–36090

    Article  CAS  PubMed  Google Scholar 

  • Hirsch T et al (2017) Regeneration of the entire human epidermis using transgenic stem cells. Nature 551(7680):327–332

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Hou P-C et al (2021) Investigational treatments for epidermolysis bullosa. Am J Clin Dermatol 22:801–817

    Article  PubMed  Google Scholar 

  • Hou Y et al (2015) Intravenously administered recombinant human type VII collagen derived from Chinese hamster ovary cells reverses the disease phenotype in recessive dystrophic epidermolysis bullosa mice. J Investig Dermatol 135(12):3060–3067

    Article  CAS  PubMed  Google Scholar 

  • Hourd P et al (2021) Regulatory challenges for the manufacture and scale-out of autologous cell therapies. Int J Biomed Health Sci 10(4)

  • Hünefeld C et al (2013) One goal, different strategies–molecular and cellular approaches for the treatment of inherited skin fragility disorders. Exp Dermatol 22(3):162–167

    Article  PubMed  Google Scholar 

  • Ito K et al (2009) Keratinocyte-/fibroblast-targeted rescue of Col7a1-disrupted mice and generation of an exact dystrophic epidermolysis bullosa model using a human COL7A1 mutation. Am J Pathol 175(6):2508–2517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaipe H et al (2015) Immunogenicity of decidual stromal cells in an epidermolysis bullosa patient and in allogeneic hematopoietic stem cell transplantation patients. Stem Cells Dev 24(12):1471–1482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kashpur O et al (2019) Differentiation of diabetic foot ulcer–derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes. FASEB J 33(1):1262–1277

    Article  CAS  PubMed  Google Scholar 

  • Kaviarasan P, Prasad PV, Shradda PV (2005) Kindler syndrome. Indian J Dermatol Venereol Leprol 71:348

    Article  CAS  PubMed  Google Scholar 

  • Kazmi B, Inglefield CJ, Lewis M (2009) Autologous cell therapy: current treatments and future prospects. Wounds 21(9):234–242

    PubMed  Google Scholar 

  • Keith AR et al (2020) Leading edge: emerging drug, cell, and gene therapies for junctional epidermolysis bullosa. Expert Opin Biol Ther 20(8):911–923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kern JS et al (2009) Mechanisms of fibroblast cell therapy for dystrophic epidermolysis bullosa: high stability of collagen VII favors long-term skin integrity. Mol Ther 17(9):1605–1615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khaniani MS et al (2015) One novel frameshift mutation on exon 64 of COL7A1 gene in an Iranian individual suffering recessive dystrophic epidermolysis bullosa. Ann Clin Lab Sci 45(5):582–584

    CAS  PubMed  Google Scholar 

  • Kho YC et al (2010) Epidemiology of epidermolysis bullosa in the antipodes: the Australasian Epidermolysis Bullosa Registry with a focus on Herlitz junctional epidermolysis bullosa. Arch Dermatol 146(6):635–640

    Article  PubMed  Google Scholar 

  • Kiritsi D et al (2011) Molecular mechanisms of phenotypic variability in junctional epidermolysis bullosa. J Med Genet 48(7):450–457

    Article  CAS  PubMed  Google Scholar 

  • Kittridge A et al (2014) Herlitz junctional epidermolysis bullosa with a novel mutation in LAMB 3. Pediatr Dermatol 31(4):530–532

    Article  PubMed  Google Scholar 

  • Kligys KR et al (2012) α6β4 integrin, a master regulator of expression of integrins in human keratinocytes. J Biol Chem 287(22):17975–17984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kocher T, Koller U (2021) Advances in gene editing strategies for epidermolysis bullosa. Prog Mol Biol Transl Sci 182:81–109

    Article  CAS  PubMed  Google Scholar 

  • Kocher T et al (2017) Cut and paste: efficient homology-directed repair of a dominant negative KRT14 mutation via CRISPR/Cas9 nickases. Mol Ther 25(11):2585–2598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kocher T et al (2019) Improved double-nicking strategies for COL7A1-editing by homologous recombination. Mol Ther Nucleic Acids 18:496–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kocher T et al (2020) Predictable CRISPR/Cas9-mediated COL7A1 reframing for dystrophic epidermolysis bullosa. J Investig Dermatol 140(10):1985–1993

    Article  CAS  PubMed  Google Scholar 

  • Koller U et al (2014) Considerations for a successful RNA trans-splicing repair of genetic disorders. Mol Ther Nucleic Acids:3

  • Kopp J et al (2005) Hematopoietic stem cell transplantation and subsequent 80% skin exchange by grafts from the same donor in a patient with Herlitz disease. Transplantation 79(2):255–256

    Article  PubMed  Google Scholar 

  • Kulkarni JA et al (2021) The current landscape of nucleic acid therapeutics. Nat Nanotechnol 16(6):630–643

    Article  CAS  PubMed  ADS  Google Scholar 

  • Kulus M et al (2021) Mesenchymal stem/stromal cells derived from human and animal perinatal tissues—origins, characteristics, signaling pathways, and clinical trials. Cells 10(12):3278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar S et al (2014) Autologous therapies in dermatology. J Clin Aesthet Dermatol 7(12):38

    PubMed  PubMed Central  Google Scholar 

  • Lai-Cheong J et al (2009a) Kindler syndrome: a focal adhesion genodermatosis. Br J Dermatol 160(2):233–242

    Article  CAS  PubMed  Google Scholar 

  • Lai-Cheong JE, McGrath JA (2010) Kindler syndrome. Dermatol Clin 28(1):119–124

    Article  CAS  PubMed  Google Scholar 

  • Lai-Cheong JE et al (2009b) Loss-of-function FERMT1 mutations in kindler syndrome implicate a role for fermitin family homolog-1 in integrin activation. Am J Pathol 175(4):1431–1441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lane E, McLean W (2004) Keratins and skin disorders. J Pathol: A J Pathol Soc Great Britain and Ireland 204(4):355–366

    Article  CAS  Google Scholar 

  • Larouche J et al (2018) Immune regulation of skin wound healing: mechanisms and novel therapeutic targets. Adv Wound Care 7(7):209–231

    Article  Google Scholar 

  • Latella MC et al (2017) Correction of recessive dystrophic epidermolysis bullosa by transposon-mediated integration of COL7A1 in transplantable patient-derived primary keratinocytes. J Investig Dermatol 137(4):836–844

    Article  CAS  PubMed  Google Scholar 

  • Lee SE et al (2021) Intravenous allogeneic umbilical cord blood–derived mesenchymal stem cell therapy in recessive dystrophic epidermolysis bullosa patients. JCI insight 6(2)

  • Lehn P et al (1998) Gene delivery systems: bridging the gap between recombinant viruses and artificial vectors. Adv Drug Deliv Rev 30(1-3):5–11

    Article  CAS  PubMed  Google Scholar 

  • Lei Y et al (2013) Generation of gene disruptions by transcription activator-like effector nucleases (TALENs) in Xenopus tropicalis embryos. Cell Biosci 3(1):1–10

    Article  ADS  Google Scholar 

  • Lukomska B et al (2019) Challenges and controversies in human mesenchymal stem cell therapy. Stem Cells Int 2019

  • March OP, Kocher T, Koller U (2020) Context-dependent strategies for enhanced genome editing of genodermatoses. Cells 9(1):112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mariath LM et al (2020) Inherited epidermolysis bullosa: update on the clinical and genetic aspects. An Bras Dermatol 95:551–569

    Article  PubMed  PubMed Central  Google Scholar 

  • Marinkovich MP, Bauer E (2008) Epidermolysis bullosa. Fitzpatrick’s dermatology in general medicine, 7th edn. McGraw-Hill, New York, pp 505–516

    Google Scholar 

  • Marinkovich MP, Tang JY (2019) Gene therapy for epidermolysis bullosa. J Investig Dermatol 139(6):1221–1226

    Article  CAS  PubMed  Google Scholar 

  • Maseda R et al (2020) Beneficial effect of systemic allogeneic adipose derived mesenchymal cells on the clinical, inflammatory and immunologic status of a patient with recessive dystrophic epidermolysis bullosa: a case report. Front Med 7:576558

    Article  Google Scholar 

  • Mathes DW et al (2014) Simultaneous transplantation of hematopoietic stem cells and a vascularized composite allograft leads to tolerance. Transplantation 98(2):131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mavilio F et al (2006) Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med 12(12):1397–1402

    Article  CAS  PubMed  Google Scholar 

  • McAllister TN, Audley D, L’Heureux N (2012) Autologous cell therapies: challenges in US FDA regulation. Regen Med 7(6 Suppl):94–97

    Article  CAS  PubMed  Google Scholar 

  • McGrath J, Eady R, Pope F (2004) Anatomy and organization of human skin. Rook’s Textbook Dermatol 1:3.2-3.80

    Google Scholar 

  • McGrath JA et al (1993) Cultured keratinocyte allografts and wound healing in severe recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol 29(3):407–419

    Article  CAS  PubMed  Google Scholar 

  • McLean WI, Smith FJ, Cassidy AJ (2005) Insights into genotype–phenotype correlation in pachyonychia congenita from the human intermediate filament mutation database. In: Journal of Investigative Dermatology Symposium Proceedings. Elsevier

    Google Scholar 

  • Melo SP et al (2014) Somatic correction of junctional epidermolysis bullosa by a highly recombinogenic AAV variant. Mol Ther 22(4):725–733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mencía Á et al (2018) Deletion of a pathogenic mutation-containing exon of COL7A1 allows clonal gene editing correction of RDEB patient epidermal stem cells. Mol Ther Nucleic Acids 11:68–78

    Article  PubMed  PubMed Central  Google Scholar 

  • Michalak A et al (2018) A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa-case report and literature review. BMC Gastroenterol 18(1):1–5

    Article  Google Scholar 

  • Moravvej H et al (2016) Comparison of the application of allogeneic fibroblast and autologous mesh grafting with the conventional method in the treatment of third-degree burns. J Burn Care Res 37(1):e90–e95

    Article  PubMed  Google Scholar 

  • Mousaei Ghasroldasht M et al (2022) Stem cell therapy: from idea to clinical practice. Int J Mol Sci 23(5):2850

    Article  PubMed  PubMed Central  Google Scholar 

  • Mullard A (2023) FDA approves first topical gene therapy. Nature reviews. Drug Discov

  • Murauer EM et al (2013) A reporter-based screen to identify potent 3’trans-splicing molecules for endogenous RNA repair. Hum Gene Ther Methods 24(1):19–27

    Article  CAS  PubMed  Google Scholar 

  • Murauer EM et al (2015) Advances in gene/cell therapy in epidermolysis bullosa. Keio J Med:2014-0013-RE

  • Murrell DF (2009) Life with epidermolysis bullosa (EB): etiology, diagnosis, multidisciplinary care and therapy. J Am Acad Dermatol 61(6):1092–1093

    Article  Google Scholar 

  • Nagy N et al (2011) HB-EGF induces COL7A1 expression in keratinocytes and fibroblasts: possible mechanism underlying allogeneic fibroblast therapy in recessive dystrophic epidermolysis bullosa. J Investig Dermatol 131(8):1771–1774

    Article  CAS  PubMed  Google Scholar 

  • Naso G, Petrova A (2020) Cellular therapy options for genetic skin disorders with a focus on recessive dystrophic epidermolysis bullosa. Br Med Bull 136(1):30–45

    Article  PubMed  Google Scholar 

  • Natsuga K et al (2021) Current topics in epidermolysis bullosa: pathophysiology and therapeutic challenges. J Dermatol Sci 104(3):164–176

    Article  CAS  PubMed  Google Scholar 

  • Niti A, Koliakos G, Michopoulou A (2023) Stem cell therapies for epidermolysis bullosa treatment. Bioengineering 10(4):422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nourian Dehkordi A et al (2019) Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies. Stem Cell Res Ther 10(1):1–20

    Article  Google Scholar 

  • Nyström A, Bernasconi R, Bornert O (2018) Therapies for genetic extracellular matrix diseases of the skin. Matrix Biol 71:330–347

    Article  PubMed  Google Scholar 

  • Nyström A, Bruckner-Tuderman L, Kern JS (2013) Cell-and protein-based therapy approaches for epidermolysis bullosa. In: Molecular Dermatology. Springer, pp 425–440

    Chapter  Google Scholar 

  • Nyström A et al (2015) Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms. EMBO Mol Med 7(9):1211–1228

    Article  PubMed  PubMed Central  Google Scholar 

  • Oever MV et al (2016) miR-29 regulates type VII collagen in recessive dystrophic epidermolysis bullosa. J Investig Dermatol 136(10):2013–2021

    Article  Google Scholar 

  • Ormond KE et al (2019) The clinical application of gene editing: ethical and social issues. Pers Med 16(4):337–350

    Article  CAS  Google Scholar 

  • Osborn MJ et al (2020) Base editor correction of COL7A1 in recessive dystrophic epidermolysis bullosa patient-derived fibroblasts and iPSCs. J Investig Dermatol 140(2):338–347

    Article  CAS  PubMed  Google Scholar 

  • Pânzaru M-C et al (2022) Epidermolysis bullosa—a different genetic approach in correlation with genetic heterogeneity. Diagnostics 12(6):1325

    Article  PubMed  PubMed Central  Google Scholar 

  • Patel PM et al (2021) A review of acquired autoimmune blistering diseases in inherited epidermolysis bullosa: implications for the future of gene therapy. Antibodies 10(02):19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peking P et al (2017) An RNA-targeted therapy for dystrophic epidermolysis bullosa. Nucleic Acids Res 45(17):10259–10269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peking P et al (2019) An ex vivo RNA trans-splicing strategy to correct human generalized severe epidermolysis bullosa simplex. Br J Dermatol 180(1):141–148

    Article  CAS  PubMed  Google Scholar 

  • Petrof G et al (2013) Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial. Br J Dermatol 169(5):1025–1033

    Article  CAS  PubMed  Google Scholar 

  • Petrof G et al (2015) Potential of systemic allogeneic mesenchymal stromal cell therapy for children with recessive dystrophic epidermolysis bullosa. J Invest Dermatol 135(9):2319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Petrof G et al (2022) The epidemiology of epidermolysis bullosa in England and Wales: data from the national epidermolysis bullosa database. Br J Dermatol 186(5):843–848

    Article  PubMed  Google Scholar 

  • Petrova A, Ilic D, McGrath J (2010) Stem cell therapies for recessive dystrophic epidermolysis bullosa. Br J Dermatol 163(6):1149–1156

    Article  CAS  PubMed  Google Scholar 

  • Pfendner E, Uitto J (2005) Plectin gene mutations can cause epidermolysis bullosa with pyloric atresia. J Investig Dermatol 124(1):111–115

    Article  CAS  PubMed  Google Scholar 

  • Pfendner, E.G. and A.W. Lucky, Junctional epidermolysis bullosa. 2018a.

    Google Scholar 

  • Pfendner, E.G. and A.W. Lucky, Dystrophic epidermolysis bullosa. 2018b.

    Google Scholar 

  • Piipponen M, Li D, Landén NX (2020) The immune functions of keratinocytes in skin wound healing. Int J Mol Sci 21(22):8790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prasongchean W, Ferretti (2012) Autologous stem cells for personalised medicine. New Biotechnol 29(6):641–650

    Article  CAS  Google Scholar 

  • Prodinger C et al (2019) Epidermolysis bullosa: advances in research and treatment. Exp Dermatol 28(10):1176–1189

    Article  PubMed  PubMed Central  Google Scholar 

  • Rashidghamat E, McGrath JA (2017) Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa. Intractable Rare Dis Res 6(1):6–20

    Article  PubMed  PubMed Central  Google Scholar 

  • Rashidghamat E et al (2020) Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol 83(2):447–454

    Article  CAS  PubMed  Google Scholar 

  • Remington J et al (2009) Injection of recombinant human type VII collagen corrects the disease phenotype in a murine model of dystrophic epidermolysis bullosa. Mol Ther 17(1):26–33

    Article  CAS  PubMed  Google Scholar 

  • Ren D et al (2022) Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy. Pharmaceutics 14(9):1973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rheinwatd JG, Green H (1975) Seria cultivation of strains of human epidemal keratinocytes: the formation keratinizin colonies from single cell is. Cell 6(3):331–343

    Article  Google Scholar 

  • Riedl J et al (2021) ABCB5+ dermal mesenchymal stromal cells with favorable skin homing and local immunomodulation for recessive dystrophic epidermolysis bullosa treatment. Stem Cells 39(7):897–903

    Article  CAS  PubMed  Google Scholar 

  • Robbins PD, Ghivizzani SC (1998) Viral vectors for gene therapy. Pharmacol Ther 80(1):35–47

    Article  CAS  PubMed  Google Scholar 

  • Rossi S et al (2021) Immunofluorescence mapping, electron microscopy and genetics in the diagnosis and sub-classification of inherited epidermolysis bullosa: a single-centre retrospective comparative study of 87 cases with long-term follow-up. J Eur Acad Dermatol Venereol 35(4):1007–1016

    Article  CAS  PubMed  Google Scholar 

  • Saunderson RB et al (2019) A retrospective cohort study evaluating the accuracy of clinical diagnosis compared with immunofluorescence and electron microscopy in children with inherited epidermolysis bullosa. Br J Dermatol 180(5):1258–1259

    Article  CAS  PubMed  Google Scholar 

  • Sayed N et al (2022) Gene therapy: comprehensive overview and therapeutic applications. Life Sci 294:120375

    Article  CAS  PubMed  Google Scholar 

  • Schwieger-Briel A et al (2015) A COL7A1 variant leading to in-frame skipping of exon 15 attenuates disease severity in recessive dystrophic epidermolysis bullosa. Br J Dermatol 173(5):1308–1311

    Article  CAS  PubMed  Google Scholar 

  • Sfeir A, Symington LS (2015) Microhomology-mediated end joining: a back-up survival mechanism or dedicated pathway? Trends Biochem Sci 40(11):701–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shahryari A et al (2019) Development and clinical translation of approved gene therapy products for genetic disorders. Front Genet 10:868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shamis Y et al (2012) iPSC-derived fibroblasts demonstrate augmented production and assembly of extracellular matrix proteins. In Vitro Cell Dev Biol Anim 48(2):112–122

    Article  CAS  PubMed  Google Scholar 

  • Shams F et al (2021) The utility of dermal fibroblasts in treatment of skin disorders: a paradigm of recessive dystrophic epidermolysis bullosa. Dermatol Ther 34(4):e15028

    Article  CAS  PubMed  Google Scholar 

  • Sharma P et al (2021) Stem cells and growth factors-based delivery approaches for chronic wound repair and regeneration: a promise to heal from within. Life Sci 268:118932

    Article  CAS  PubMed  Google Scholar 

  • Shinkuma S (2015) Dystrophic epidermolysis bullosa: a review. Clin Cosmet Investig Dermatol 8:275

    Article  PubMed  PubMed Central  Google Scholar 

  • Siprashvili Z et al (2010) Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue. Hum Gene Ther 21(10):1299–1310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siprashvili Z et al (2016) Safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with recessive dystrophic epidermolysis bullosa. Jama 316(17):1808–1817

    Article  PubMed  Google Scholar 

  • Siprashvili Z et al (2017) Phase I/IIa clinical trial for recessive dystrophic epidermolysis bullosa using genetically corrected autologous keratinocytes. J Invest Dermatol 137(5 Suppl. 1):S89

    Article  Google Scholar 

  • Solis DC et al Classification of two distinct wound types in recessive dystrophic epidermolysis bullosa: a retrospective and cohort natural history study. J Am Acad Dermatol 85(5):1296–1298

  • Sorg H et al (2017) Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res 58(1-2):81–94

    Article  PubMed  Google Scholar 

  • Stublar A, Dragos V, Dolenc-Voljc M (2021) Inherited epidermolysis bullosa: epidemiology and patient care in Slovenia with a review of the updated classification. Acta Dermatovenerol Alp Panon Adriat 30(2):63–67

    Google Scholar 

  • Sugawara K et al (2008) Laminin-332 and-511 in skin. Exp Dermatol 17(6):473–480

    Article  CAS  PubMed  Google Scholar 

  • Takeichi T et al (2015) Founder mutation in dystonin-e underlying autosomal recessive epidermolysis bullosa simplex in Kuwait. Br J Dermatol 172(2):527–531

    Article  CAS  PubMed  Google Scholar 

  • Tamai K, Uitto J (2016) Stem cell therapy for epidermolysis bullosa—does it work? J Investig Dermatol 136(11):2119–2121

    Article  CAS  PubMed  Google Scholar 

  • Tamai K et al (2011) PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia. Proc Natl Acad Sci 108(16):6609–6614

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  • Tang JY et al (2021) A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa. Orphanet J Rare Dis 16(1):1–25

    Article  MathSciNet  Google Scholar 

  • Techanukul T et al (2011) Novel and recurrent FERMT1 gene mutations in Kindler syndrome. Acta Derm Venereol 91(3):267

    Article  PubMed  Google Scholar 

  • Titeux M et al (2020) Emerging drugs for the treatment of epidermolysis bullosa. Expert Opin Emerg Drugs 25(4):467–489

    Article  CAS  PubMed  Google Scholar 

  • Tockner B et al (2016) Construction and validation of an RNA trans-splicing molecule suitable to repair a large number of COL7A1 mutations. Gene Ther 23(11):775–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tolar J, Blazar BR, Wagner JE (2011) Concise review: transplantation of human hematopoietic cells for extracellular matrix protein deficiency in epidermolysis bullosa. Stem Cells 29(6):900–906

    Article  PubMed  Google Scholar 

  • Tolar J, Wagner JE (2012) Management of severe epidermolysis bullosa by haematopoietic transplant: principles, perspectives and pitfalls. Exp Dermatol 21(12):896–900

    Article  PubMed  Google Scholar 

  • Tolar J, Wagner JE (2015) A biologic Velcro patch. N Engl J Med 372(4):382–384

    Article  CAS  PubMed  Google Scholar 

  • Tolar J et al (2009) Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells. Blood, J Am Soc Hematol 113(5):1167–1174

    CAS  Google Scholar 

  • Tong Y, Zuo J, Yue D (2021) Application prospects of mesenchymal stem cell therapy for bronchopulmonary dysplasia and the challenges encountered. Biomed Res Int 2021

  • Turczynski, S., et al., Antisense-mediated exon skipping to reframe transcripts. Exon Skipping: Methods and Protocols, 2012: 221-238.

  • Uitto J et al (2010) Progress in epidermolysis bullosa research: toward treatment and cure. J Investig Dermatol 130(7):1778–1784

    Article  CAS  PubMed  Google Scholar 

  • Uitto J et al (2016) Progress toward treatment and cure of epidermolysis bullosa: summary of the DEBRA International Research Symposium EB2015. J Investig Dermatol 136(2):352–358

    Article  CAS  PubMed  Google Scholar 

  • Uitto J et al (2018) EB2017—progress in epidermolysis bullosa research toward treatment and cure. J Investig Dermatol 138(5):1010–1016

    Article  CAS  PubMed  Google Scholar 

  • Vahidnezhad H et al (2017) Dystrophic epidermolysis bullosa: COL7A1 mutation landscape in a multi-ethnic cohort of 152 extended families with high degree of customary consanguineous marriages. J Investig Dermatol 137(3):660–669

    Article  CAS  PubMed  Google Scholar 

  • Vahidnezhad H et al (2019) Phenotypic spectrum of epidermolysis bullosa: the paradigm of syndromic versus non-syndromic skin fragility disorders. J Investig Dermatol 139(3):522–527

    Article  CAS  PubMed  Google Scholar 

  • Vanden Oever M et al (2018) Inside out: regenerative medicine for recessive dystrophic epidermolysis bullosa. Pediatr Res 83(1):318–324

    Article  Google Scholar 

  • Vander Beken S et al (2019) Newly defined ATP-binding cassette subfamily B member 5 positive dermal mesenchymal stem cells promote healing of chronic iron-overload wounds via secretion of interleukin-1 receptor antagonist. Stem Cells 37(8):1057–1074

    Article  CAS  PubMed  Google Scholar 

  • Varki R et al (2006) Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants. J Med Genet 43(8):641–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Večerić-Haler Ž et al (2021) Multiorgan failure with fatal outcome after stem cell tourism. Eur J Med Res 26(1):1–5

    Article  Google Scholar 

  • Venugopal SS et al (2013) A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol 69(6):898–908

    Article  CAS  PubMed  Google Scholar 

  • Virtanen I et al (1996) Laminin chains in the basement membranes of human thymus. Histochem J 28:643–650

    Article  CAS  PubMed  Google Scholar 

  • Vivinus-Nebot MN et al (2004) Mature human thymocytes migrate on laminin-5 with activation of metalloproteinase-14 and cleavage of CD44. J Immunol 172(3):1397–1406

    Article  CAS  PubMed  Google Scholar 

  • Wagner JE et al (2010) Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med 363(7):629–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wally V et al (2008) 5′ trans-splicing repair of the PLEC1 gene. J Investig Dermatol 128(3):568–574

    Article  CAS  PubMed  Google Scholar 

  • Wang R et al (2022) Novel variants in LAMA3 and COL7A1 and recurrent variant in KRT5 underlying epidermolysis bullosa in five Chinese families. Front Med:1–7

  • Wang X (2014) The roles of type VII collagen in wound healing and scar reduction. University of Southern California

    Google Scholar 

  • Weber F et al (2001) Squamous cell carcinoma in junctional and dystrophic epidermolysis bullosa. Acta Derm Venereol 81(3)

  • Wong T et al (2008) Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J Investig Dermatol 128(9):2179–2189

    Article  CAS  PubMed  Google Scholar 

  • Woodley DT et al (2004) Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa. Nat Med 10(7):693–695

    Article  CAS  PubMed  Google Scholar 

  • Woodley DT et al (2007) Intravenously injected human fibroblasts home to skin wounds, deliver type VII collagen, and promote wound healing. Mol Ther 15(3):628–635

    Article  CAS  PubMed  Google Scholar 

  • Woodley DT et al (2013) Intravenously injected recombinant human type VII collagen homes to skin wounds and restores skin integrity of dystrophic epidermolysis bullosa. J Invest Dermatol 133(7):1910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wright JT, Fine J, Johnson L (1993) Hereditary epidermolysis bullosa: oral manifestations and dental management. Pediatr Dent 15:242–242

    CAS  PubMed  Google Scholar 

  • Wu T-L, Ertl HC (2009) Immune barriers to successful gene therapy. Trends Mol Med 15(1):32–39

    Article  CAS  PubMed  Google Scholar 

  • Wu Y et al (2007) Bone marrow-derived stem cells in wound healing: a review. Wound Repair Regen 15:S18–S26

    Article  PubMed  ADS  Google Scholar 

  • Yamada N, Shioya N, Kuroyanagi Y (1995) Evaluation of an allogeneic cultured dermal substitute composed of fibroblasts within a spongy collagen matrix as a wound dressing. Scand J Plast Reconstr Surg Hand Surg 29(3):211–219

    Article  CAS  PubMed  Google Scholar 

  • Yenamandra V et al (2018) Cardiomyopathy in patients with epidermolysis bullosa simplex with mutations in KLHL24. Br J Dermatol 179(5):1181–1183

    Article  CAS  PubMed  Google Scholar 

  • Youssefian, L., H. Vahidnezhad, and J. Uitto, Kindler syndrome synonym: congenital bullous poikiloderma. 2016, Seattle: Pagon RA, Adam MP, Ardinger HH, et al.

  • Youssefian, L., H. Vahidnezhad, and J. Uitto, Kindler syndrome. 2022.

    Google Scholar 

  • Youssefian L et al (2015) The Kindler syndrome: a spectrum of FERMT1 mutations in Iranian families. J Invest Dermatol 135(5):1447–1450

    Article  CAS  PubMed  Google Scholar 

  • Zhang X et al (2017) CRISPR/Cas9 system: a powerful technology for in vivo and ex vivo gene therapy. Sci China Life Sci 60(5):468–475

    Article  CAS  PubMed  ADS  Google Scholar 

  • Zidorio A et al (2018) Effectiveness of gastrostomy for improving nutritional status and quality of life in patients with epidermolysis bullosa: a systematic review. Br J Dermatol 179(1):42–49

    Article  CAS  PubMed  Google Scholar 

Download references

Availability of data and material

Not applicable.

Funding

This study is financially supported by the student research committee of Behbahan Faculty of Medical Sciences (Grant Number: 402042).

Author information

Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Fatemeh Gila

  2. Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Vahab Alamdari-Palangi & Jafar Fallahi

  3. Department of Veterinary Sciences, University of Wyoming, Laramie, WY, USA

    Maedeh Rafiee

  4. Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Arezoo Jokar

  5. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sajad Ehtiaty & Seyyed Hossein Khatami

  6. Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Aria Dianatinasab

  7. Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran

    Mortaza Taheri-Anganeh

  8. Behbahan Faculty of Medical Sciences, Behbahan, Iran

    Ahmad Movahedpour

Authors
  1. Fatemeh Gila
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vahab Alamdari-Palangi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maedeh Rafiee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arezoo Jokar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sajad Ehtiaty
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aria Dianatinasab
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seyyed Hossein Khatami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mortaza Taheri-Anganeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ahmad Movahedpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jafar Fallahi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Writing and drafting: Fatemeh Gila, Vahab Alamdari-Palangi, Maedeh Rafiee, Arezoo Jokar, and Sajad Ehtiaty. Data curation: Aria Dianatinasab, Seyyed Hossein Khatami, and Mortaza Taheri-Anganeh. Conceptualization: Jafar Fallahi. Supervision: Ahmad Movahedpour.

Corresponding authors

Correspondence to Ahmad Movahedpour or Jafar Fallahi.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by: Ewa Ziętkiewicz

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gila, F., Alamdari-Palangi, V., Rafiee, M. et al. Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa. J Appl Genetics (2024). https://doi.org/10.1007/s13353-024-00839-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13353-024-00839-2

Keywords

Search

Navigation