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Human Stromal Stem Cell Therapy Using Gene-Modified Cells

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Somatic Genome Manipulation

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Abstract

There is an increasing demand to develop novel approaches for the treatment of a large number of chronic degenerative diseases affecting primarily the aging population and where there is currently no effective therapy, e.g., Parkinson’s disease, liver failure, diabetes, osteoarthritis, and osteoporosis. An emerging therapeutic approach for the management of these conditions is cell therapy or cellular therapeutics where organ functions are restored through transplanting healthy, functional cells. Stem cells, because of their nature, are currently considered the most suitable cells for cell therapy. As mentioned in other chapters in this book, gene therapy aims at modifying specific characteristics of target cells with possible therapeutic effects. Thus, combining gene therapy with stem cell therapy provides an additional useful dimension to the use of stem cells for treatment. Stromal (mesenchymal) stem cells are being introduced into clinical trials due to their ease of isolation and efficacy in treating a number of disease conditions in animal preclinical disease models. Also, there are an increasing number of studies that have tested the genetically modified mesenchymal stem cells (MSC) functionality in vivo. The aim of this chapter is to review the potential use of gene-modified stem cells, in particular gene-modified MSC, in therapy and the challenges facing their use in clinical practice.

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Abbreviations

Runx2:

Runt-related transcription factor 2

BMB2:

Bone morphogenetic protein 2

HIF-1α:

Hypoxia-inducible factor 1, α subunit

Osx:

Osterix

IGF-1:

Insulin-like growth factor 1

VEGF:

Vascular endothelial growth factor

Akt:

Protein kinase B

ANG1:

Angiopoietin 1

BCL2:

B cell lymphoma 2

SDF1:

Stromal-derived factor 1

TNF:

Tumor necrosis factor

CXCR4:

Chemokine receptor type 4

NICD:

Notch intracellular domain

GLP-1:

Glucagon-like peptide 1

IFN-α:

Interferon-α

IFN-β:

Interferon-β

IL-2:

Interleukin 2

IL12:

Interleukin 12

CCr1:

Chemokine receptor type 1

References

  • Abdallah BM, Kassem M (2009) The use of mesenchymal (skeletal) stem cells for treatment of degenerative diseases: current status and future perspectives. J Cell Physiol 218:9–12

    Article  CAS  PubMed  Google Scholar 

  • Abdallah BM, Haack-Sorensen M, Burns JS, Elsnab B, Jakob F, Hokland P, Kassem M (2005) Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene despite [corrected] extensive proliferation. Biochem Biophys Res Commun 326:527–538

    Article  CAS  PubMed  Google Scholar 

  • Abdallah BM, Ditzel N, Kassem M (2008) Assessment of bone formation capacity using in vivo transplantation assays: procedure and tissue analysis. Methods Mol Biol 455:89–100

    Article  PubMed  Google Scholar 

  • Ahlmann E, Patzakis M, Roidis N, Shepherd L, Holtom P (2002) Comparison of anterior and posterior iliac crest bone grafts in terms of harvest-site morbidity and functional outcomes. J Bone Joint Surg Am 84-A:716–720

    PubMed  Google Scholar 

  • Al-Nbaheen M, Vishnubalaji R, Ali D, Bouslimi A, Al-Jassir F, Megges M, Prigione A, Adjaye J, Kassem M, Aldahmash A (2012) Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential. Stem Cell Rev 9(1):32–43

    Article  PubMed Central  Google Scholar 

  • Bentzon JF, Stenderup K, Hansen FD, Schroder HD, Abdallah BM, Jensen TG and Kassem M (2005) Tissue distribution and engraftment of human mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene. Biochem Biophys Res Commun 330:633–640

    Article  CAS  PubMed  Google Scholar 

  • Bertani N, Malatesta P, Volpi G, Sonego P, Perris R (2005) Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, time-lapse video and microarray. J Cell Sci 118:3925–3936

    Article  CAS  PubMed  Google Scholar 

  • Carano RA, Filvaroff EH (2003) Angiogenesis and bone repair. Drug DiscovToday 8:980–989

    CAS  Google Scholar 

  • Chamberlain G, Wright K, Rot A, Ashton B, Middleton J (2008) Murine mesenchymal stem cells exhibit a restricted repertoire of functional chemokine receptors: comparison with human. PLoS One 3:e2934

    Article  PubMed Central  PubMed  Google Scholar 

  • Chen D, Zhao M, Mundy GR (2004) Bone morphogenetic proteins. Growth Factors 22:233–241

    Article  CAS  PubMed  Google Scholar 

  • Cheng Z, Ou L, Zhou X, Li F, Jia X, Zhang Y, Liu X, Li Y, Ward CA, Melo LG, Kong D (2008) Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther 16:571–579

    Article  CAS  PubMed  Google Scholar 

  • De Bari C Dell'Accio F Tylzanowski P Luyten FP (2001) Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 44:1928–1942

    Article  CAS  PubMed  Google Scholar 

  • De Coppi P Bartsch G Jr. Siddiqui MM Xu T Santos CC Perin L Mostoslavsky G Serre AC Snyder EY Yoo JJ Furth ME Soker S Atala A (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25:100–106

    Article  CAS  PubMed  Google Scholar 

  • Devine MJ, Mierisch CM, Jang E, Anderson PC, Balian G (2002) Transplanted bone marrow cells localize to fracture callus in a mouse model. J Orthop Res 20:1232–1239

    Article  PubMed  Google Scholar 

  • Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, Tajima N, Yamada H, Sawada H, Ishikawa H, Mimura T, Kitada M, Suzuki Y, Ide C (2004) Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest 113:1701–1710

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Emms NW, Buckley SC, Stockley I, Hamer AJ, Kerry RM (2009) Mid- to long-term results of irradiated allograft in acetabular reconstruction: a follow-up report. J Bone Joint Surg Br 91:1419–1423

    Article  CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403

    CAS  PubMed  Google Scholar 

  • Fuster V, Kelly BB, Vedanthan R (2011) Global cardiovascular health: urgent need for an intersectoral approach. J Am Coll Cardiol 58:1208–1210

    Article  PubMed  Google Scholar 

  • Galloway SM, McNatty KP, Cambridge LM, Laitinen MP, Juengel JL, Jokiranta TS, McLaren RJ, Luiro K, Dodds KG, Montgomery GW, Beattie AE, Davis GH, Ritvos O (2000) Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet 25:279–283

    Article  CAS  PubMed  Google Scholar 

  • Grauss RW, Winter EM, van TJ, Pijnappels DA, Steijn RV, Hogers B, van der Geest RJ, de Vries AA, Steendijk P, van der Laarse A, Gittenberger-de Groot AC, Schalij MJ, Atsma DE (2007) Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction. Am J Physiol Heart Circ Physiol 293:H2438–H2447

    Article  CAS  PubMed  Google Scholar 

  • Haider HK, Jiang S, Idris NM, Ashraf M (2008) IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha/CXCR4 signaling to promote myocardial repair. Circ Res 103:1300–1308

    Article  CAS  PubMed  Google Scholar 

  • Hanna J, Saha K, Pando B, van ZJ, Lengner CJ, Creyghton MP, van OA, Jaenisch R (2009) Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462:595–601

    Google Scholar 

  • Heile AM, Wallrapp C, Klinge PM, Samii A, Kassem M, Silverberg G, Brinker T (2009) Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury. Neurosci Lett 463:176–181

    Article  CAS  PubMed  Google Scholar 

  • Ho QT, Kuo CJ (2007) Vascular endothelial growth factor: biology and therapeutic applications. Int J Biochem Cell Biol 39:1349–1357

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Holst JJ (2004) On the physiology of GIP and GLP-1. Horm Metab Res 36:747–754

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Zhang Z, Guo J, Ni A, Deb A, Zhang L, Mirotsou M, Pratt RE, Dzau VJ (2010) Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium. Circ Res 106:1753–1762

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ingersoll SB, Ahmad S, Finkler NJ, Edwards JR, Holloway RW (2012) Cellular therapy for ovarian cancer: experimental and clinical perspectives. Curr Med Chem 19(22):3787–3793

    Article  CAS  PubMed  Google Scholar 

  • Jensen MB, Yan H, Krishnaney-Davison R, Al SA, Zhang SC (2011) Survival and differentiation of transplanted neural stem cells derived from human induced pluripotent stem cells in a rat stroke model. J Stroke Cerebrovasc Dis 22(4):304–308

    Article  PubMed Central  PubMed  Google Scholar 

  • Johnson EE, Urist MR, Finerman GA (1992) Resistant nonunions and partial or complete segmental defects of long bones. Treatment with implants of a composite of human bone morphogenetic protein (BMP) and autolyzed, antigen-extracted, allogeneic (AAA) bone. Clin Orthop Relat Res:229–237

    Google Scholar 

  • Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells 43. Exp Cell Res 238:265–272

    Article  CAS  PubMed  Google Scholar 

  • Kanczler JM, Ginty PJ, White L, Clarke NM, Howdle SM, Shakesheff KM and Oreffo RO (2010) The effect of the delivery of vascular endothelial growth factor and bone morphogenic protein-2 to osteoprogenitor cell populations on bone formation. Biomaterials 31:1242–1250

    Article  CAS  PubMed  Google Scholar 

  • Karp JM, Leng Teo GS (2009) Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 4:206–216

    Article  CAS  PubMed  Google Scholar 

  • Kassem M, Mosekilde L, Eriksen EF (1993) 1,25-dihydroxyvitamin D3 potentiates fluoride-stimulated collagen type I production in cultures of human bone marrow stromal osteoblast-like cells. J Bone Miner Res 8:1453–1458

    Article  CAS  PubMed  Google Scholar 

  • Keller G (2005) Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev 19:1129–1155

    Article  CAS  PubMed  Google Scholar 

  • Khoo ML, Shen B, Tao H, Ma DD (2008) Long-term serial passage and neuronal differentiation capability of human bone marrow mesenchymal stem cells. Stem Cells Dev 17:883–896

    Article  CAS  PubMed  Google Scholar 

  • Klinge PM, Harmening K, Miller MC, Heile A, Wallrapp C, Geigle P, Brinker T (2011) Encapsulated native and glucagon-like peptide-1 transfected human mesenchymal stem cells in a transgenic mouse model of Alzheimer’s disease. Neurosci Lett 497:6–10

    Article  CAS  PubMed  Google Scholar 

  • Kneser U, Schaefer DJ, Polykandriotis E, Horch RE (2006) Tissue engineering of bone: the reconstructive surgeon’s point of view. J Cell Mol Med 10:7–19

    Article  CAS  PubMed  Google Scholar 

  • Kodach LL, Wiercinska E, de Miranda NF, Bleuming SA, Musler AR, Peppelenbosch MP, Dekker E, van den Brink GR, van Noesel CJ, Morreau H, Hommes DW, Ten DP, Offerhaus GJ, Hardwick JC (2008) The bone morphogenetic protein pathway is inactivated in the majority of sporadic colorectal cancers. Gastroenterology 134:1332–1341

    Article  CAS  PubMed  Google Scholar 

  • Krabbe C, Zimmer J, Meyer M (2005) Neural transdifferentiation of mesenchymal stem cells—a critical review. APMIS 113:831–844.

    Article  PubMed  Google Scholar 

  • Kruck S, Bedke J, Kuczyk MA, Merseburger AS (2012) Second-line systemic therapy for the treatment of metastatic renal cell cancer. Expert Rev Anticancer Ther 12:777–785

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Nagy TR, Ponnazhagan S (2010a) Therapeutic potential of genetically modified adult stem cells for osteopenia. Gene Ther 17:105–116

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kumar S, Wan C, Ramaswamy G, Clemens TL, Ponnazhagan S (2010b) Mesenchymal stem cells expressing osteogenic and angiogenic factors synergistically enhance bone formation in a mouse model of segmental bone defect. Mol Ther 18:1026–1034.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kuznetsov SA, Krebsbach PH, Satomura K, Kerr J, Riminucci M, Benayahu D, Robey PG (1997) Single-colony derived strains of human marrow stromal fibroblasts form bone after transplantation in vivo. J Bone Miner Res 12:1335–1347

    Article  CAS  PubMed  Google Scholar 

  • Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG (2001) Circulating skeletal stem cells. J Cell Biol 153:1133–1140

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lepperdinger G, Brunauer R, Jamnig A, Laschober G, Kassem M (2008) Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies? Exp Gerontol 43:1018–1023

    Article  CAS  PubMed  Google Scholar 

  • Li W, Ma N, Ong LL, Nesselmann C, Klopsch C, Ladilov Y, Furlani D, Piechaczek C, Moebius JM, Lutzow K, Lendlein A, Stamm C, Li RK, Steinhoff G (2007) Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells 25:2118–2127

    Article  CAS  PubMed  Google Scholar 

  • Lien CY, Chih-Yuan HK, Lee OK, Blunn GW, Su Y (2009) Restoration of bone mass and strength in glucocorticoid-treated mice by systemic transplantation of CXCR4 and cbfa-1 co-expressing mesenchymal stem cells. J Bone Miner Res 24:837–848

    Article  CAS  PubMed  Google Scholar 

  • Luria EA, Panasyuk AF, Friedenstein AY (1971) Fibroblast colony formation from monolayer cultures of blood cells. Transfusion 11:345–349

    Article  CAS  PubMed  Google Scholar 

  • Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, Dzau VJ (2003) Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9:1195–1201

    Article  CAS  PubMed  Google Scholar 

  • McGrail DJ, Ghosh D, Quach ND, Dawson MR (2012) Differential mechanical response of mesenchymal stem cells and fibroblasts to tumor-secreted soluble factors. PLoS One 7:e33248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Menon LG, Picinich S, Koneru R, Gao H, Lin SY, Koneru M, Mayer-Kuckuk P, Glod J, Banerjee D (2007) Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells. Stem Cells 25:520–528

    Article  CAS  PubMed  Google Scholar 

  • Menon LG, Shi VJ, Carroll RS (2008) Mesenchymal stromal cells as a drug delivery system. Harvard Stem Cell Institute, Cambridge

    Google Scholar 

  • Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, Shi S (2003) SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA 100:5807–5812

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nakamura K, Ito Y, Kawano Y, Kurozumi K, Kobune M, Tsuda H, Bizen A, Honmou O, Niitsu Y, Hamada H (2004) Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Ther 11:1155–1164

    Article  CAS  PubMed  Google Scholar 

  • Omori R, Eguchi J, Hiroishi K, Ishii S, Hiraide A, Sakaki M, Doi H, Kajiwara A, Ito T, Kogo M, Imawari M (2012) Effects of interferon-alpha-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors. Cancer Gene Ther 19(9):637–643

    Article  CAS  PubMed  Google Scholar 

  • Perry TA, Greig NH (2004) A new Alzheimer’s disease interventive strategy: GLP-1. Curr Drug Targets 5:565–571

    Article  CAS  PubMed  Google Scholar 

  • Peterson B, Zhang J, Iglesias R, Kabo M, Hedrick M, Benhaim P, Lieberman JR (2005) Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue. Tissue Eng 11:120–129

    Article  CAS  PubMed  Google Scholar 

  • Plath K, Lowry WE (2011) Progress in understanding reprogramming to the induced pluripotent state. Nat Rev Genet 12:253–265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pollock K, Stroemer P, Patel S, Stevanato L, Hope A, Miljan E, Dong Z, Hodges H, Price J, Sinden JD (2006) A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke. Exp Neurol 199:143–155

    Article  PubMed  Google Scholar 

  • Ren C, Kumar S, Chanda D, Chen J, Mountz JD, Ponnazhagan S (2008a) Therapeutic potential of mesenchymal stem cells producing interferon-alpha in a mouse melanoma lung metastasis model. Stem Cells 26:2332–2338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ren C, Kumar S, Chanda D, Kallman L, Chen J, Mountz JD, Ponnazhagan S (2008b) Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model. Gene Ther 15:1446–1453

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rickard DJ, Kassem M, Hefferan TE, Sarkar G, Spelsberg TC, Riggs BL (1996) Isolation and characterization of osteoblast precursor cells from human bone marrow. J Bone Miner Res 11:312–324

    Article  CAS  PubMed  Google Scholar 

  • Rosada C, Justesen J, Melsvik D, Ebbesen P, Kassem M (2003) The human umbilical cord blood: a potential source for osteoblast progenitor cells. Calcif Tissue Int 72:135–142

    Article  CAS  PubMed  Google Scholar 

  • Sackstein R, Merzaban JS, Cain DW, Dagia NM, Spencer JA, Lin CP, Wohlgemuth R (2008) Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat Med 14:181–187

    Article  CAS  PubMed  Google Scholar 

  • Salazar DL, Uchida N, Hamers FP, Cummings BJ, Anderson AJ (2010) Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model. PLoS One 5:e12272

    Article  PubMed Central  PubMed  Google Scholar 

  • Sarkar K, Fox-Talbot K, Steenbergen C, Bosch-Marce M, Semenza GL (2009) Adenoviral transfer of HIF-1alpha enhances vascular responses to critical limb ischemia in diabetic mice. Proc Natl Acad Sci USA 106:18769–18774.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Seo SH, Kim KS, Park SH, Suh YS, Kim SJ, Jeun SS, Sung YC (2011) The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity. Gene Ther 18:488–495

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shen FH, Visger JM, Balian G, Hurwitz SR, Diduch DR (2002) Systemically administered mesenchymal stromal cells transduced with insulin-like growth factor-I localize to a fracture site and potentiate healing. J Orthop Trauma 16:651–659

    Article  PubMed  Google Scholar 

  • Shiojima I, Walsh K (2006) Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev 20:3347–3365

    Article  CAS  PubMed  Google Scholar 

  • Shujia J, Haider HK, Idris NM, Lu G, Ashraf M (2008) Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair. Cardiovasc Res 77:525–533

    Article  CAS  PubMed  Google Scholar 

  • Simonsen JL, Rosada C, Serakinci N, Justesen J, Stenderup K, Rattan SI, Jensen TG, Kassem M (2002) Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol 20:592–596

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Wang J, Zheng F, Kong X, Guo L, Yang J, Zhang L, Huang Y (2010) Combination of chemokine and angiogenic factor genes and mesenchymal stem cells could enhance angiogenesis and improve cardiac function after acute myocardial infarction in rats. Mol Cell Biochem 339:107–118

    Article  CAS  PubMed  Google Scholar 

  • Tao Z, Chen B, Tan X, Zhao Y, Wang L, Zhu T, Cao K, Yang Z, Kan YW, Su H (2011) Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart. Proc Natl Acad Sci U S A 108:2064–2069

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Tu Q, Valverde P, Li S, Zhang J, Yang P, Chen J (2007) Osterix overexpression in mesenchymal stem cells stimulates healing of critical-sized defects in murine calvarial bone. Tissue Eng 13:2431–2440

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wislet-Gendebien S, Laudet E, Neirinckx V, Alix P, Leprince P, Glejzer A, Poulet C, Hennuy B, Sommer L, Shakhova O, Rogister B (2012) Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences. Cell Mol Life Sci 69:2593–2608

    Article  CAS  PubMed  Google Scholar 

  • Wojtowicz AM, Templeman KL, Hutmacher DW, Guldberg RE, Garcia AJ (2010) Runx2 overexpression in bone marrow stromal cells accelerates bone formation in critical-sized femoral defects. Tissue Eng Part A 16:2795–2808

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wu Y, Zhao RC (2012) The role of chemokines in mesenchymal stem cell homing to myocardium. Stem Cell Rev 8:243–250

    Article  CAS  PubMed  Google Scholar 

  • Wynn RF, Hart CA, Corradi-Perini C, O'Neill L, Evans CA, Wraith JE, Fairbairn LJ, Bellantuono I (2004) A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood 104:2643–2645

    Article  CAS  PubMed  Google Scholar 

  • Zhang D, Fan GC, Zhou X, Zhao T, Pasha Z, Xu M, Zhu Y, Ashraf M, Wang Y (2008) Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol 44:281–292

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao Z, Zhao M, Xiao G, Franceschi RT (2005) Gene transfer of the Runx2 transcription factor enhances osteogenic activity of bone marrow stromal cells in vitro and in vivo. Mol Ther 12:247–253

    Article  CAS  PubMed  Google Scholar 

  • Zou D, Zhang Z, Ye D, Tang A, Deng L, Han W, Zhao J, Wang S, Zhang W, Zhu C, Zhou J, He J, Wang Y, Xu F, Huang Y, Jiang X (2011) Repair of critical-sized rat calvarial defects using genetically engineered bone marrow-derived mesenchymal stem cells overexpressing hypoxia-inducible factor-1alpha. Stem Cells 29:1380–1390

    CAS  PubMed  Google Scholar 

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Acknowledgments

We acknowledge the support of grants from the Lundbeck foundation (Denmark), NovoNordisk foundation (Denmark), and KACST (Project Code: 10-BIO1308–02) (KSA).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital, University of Southern Denmark, Kloevervaenget 6, 4th floor, 5000, Odense, Denmark

    Prof. Walid Zaher & Moustapha Kassem

  2. DanStem (Danish stem cell center), Panum Institute, University of Copenhagen, Copenhagen, Denmark

    Moustapha Kassem

  3. Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Prof. Walid Zaher

Authors
  1. Prof. Walid Zaher
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  2. Moustapha Kassem
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Correspondence to Moustapha Kassem .

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Editors and Affiliations

  1. Potato Research Centre, Agriculture and Agri-Food Canada, Government of Canada, Fredericton, New Brunswick, Canada

    Xiu-Qing Li

  2. Plant Science Department, McGill University, Sainte-Anne-de-Bellevue, Québec, Canada

    Danielle J. Donnelly

  3. Department of Biomedicine, Aarhus University, Herning, Denmark

    Thomas G. Jensen

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Zaher, W., Kassem, M. (2015). Human Stromal Stem Cell Therapy Using Gene-Modified Cells. In: Li, XQ., Donnelly, D., Jensen, T. (eds) Somatic Genome Manipulation. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2389-2_5

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