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Human Mesenchymal Stem Cells: The Art to Use Them in the Treatment of Previously Untreatable

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Handbook of Stem Cell Therapy

Abstract

Mesenchymal stem cells (MSCs) can be isolated from almost all organs and tissues in the human body. For practical purposes, there are two main sources for their isolation and ex vivo expansion – the bone marrow and fat tissue. Based on their inherent plastic adherence properties, the ex vivo expansion of MSCs is a rather simple process. Nevertheless, the biological features (gained from decades of tissue culture experience) are contrary to bureaucratic rules, which govern the good laboratory practice. MSCs cannot be successfully used in the treatment of human diseases if they are not handled optimally akin to the conditions in their natural habitat. Moreover, extrapolation of the data obtained from animal studies (mainly rodents) to humans is unfounded and with little relevance. The therapeutic use of genetically manipulated MSCs in human can be even harmful to patients. The current research paradigm, i.e., the use of MSCs in advanced phases of clinical trials although understandable, is far from personalized medical approach. The use of allogeneic versus autologous MSC in the clinical perspective is still debatable. There is growing evidence that the autologous MSCs derived from sick patients are “ill” in contrast to MSCs derived from healthy allogeneic donors. One can observe various changes at the DNA, RNA, and protein level in these “ill” cells. However, the huge number of cells from ex vivo expanded autologous MSCs can, possibly, overcome these aberrations. The off-the-shelf availability of allogenic MSCs also contributes to their logistic superiority over autologous cells. Moreover, due to almost non-existing immunological barriers, allogenic MSCs are emerging as gold standard and near-optimal cell types for the treatment of various diseases in humans. This chapter reviews the authors experience(s) in the treatment of various diseases with autologous/allogenic MSCs handled optimally ex vivo.

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Abbreviations

DMEM-LG:

Dulbecco’s modified Eagle medium, low glucose

GMP:

Good Manufacturing Practices

GVDH:

Graft-versus-host disease

LG:

Low glucose

LVAD:

Left ventricular assist device

MSCs:

Mesenchymal stem cells

NYHA:

New York Heart Association

References

  • Ambrosi TH, Scialdone A, Graja A et al (2017) Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell 20(6):771–784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antebi B, Asher AM, Rodriguez LA, Moore RK, Mohammadipoor A, Cancio LC (2019) Cryopreserved mesenchymal stem cells regain functional potency following a 24-h acclimation period. J Transl Med 17:297. https://doi.org/10.1186/s12967-019-2038-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asari S, Itakura S, Ferreri K, Liu CP, Kuroda Y, Kandeel F, Mullen Y (2009) Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol 37(5):604–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beitnes JO, Øie E, Shahdadfar A, Karlsen T, Müller RMB, Aakhus S, Reinholt FP, Brinchmann JE (2012) Intramyocardial injections of human mesenchymal stem cells following acute myocardial infarction modulate scar formation and improve left ventricular function. Cell Transplant 21:1697–1709. https://doi.org/10.3727/096368911X627462

    Article  Google Scholar 

  • Bonab MM, Alimoghaddam K, Talebian F, Ghaffari H, Ghavamzadeh A, Nikbin B (2006) Aging of mesenchymal stem cell in vitro. BMC Cell Biol 7:14

    Article  PubMed  PubMed Central  Google Scholar 

  • Bustos ML, Huleihel L, Kapetanaki MG, Lino-Cardenas CL, Mroz L, Ellis BM, McVerry BJ et al (2014) Aging mesenchymal stem cells fail to protect because of impaired migration and antiinflammatory response. Am J Respir Crit Care Med 189(7):787–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cesselli D, Beltrami AP, D’Aurizio F, Marcon P, Bergamin N, Toffoletto B, Pandolfi M (2011) Effects of age and heart failure on human cardiac stem cell function. Am J Pathol 179(1):349–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen C-H, Chang M-Y, Wang S-S, Hsieh PCH (2014) Injection of autologous bone marrow cells in hyaluronan hydrogel improves cardiac performance after infarction in pigs. Am J Physiol Heart Circ Physiol 306(7):H1078–H1086

    Article  CAS  PubMed  Google Scholar 

  • Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, Risso M et al (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107(1):367–372

    Article  CAS  PubMed  Google Scholar 

  • Cui L-L, Kinnunen T, Boltze J, Nystedt J, Jolkkonen J (2016) Clumping and viability of bone marrow derived mesenchymal stromal cells under different preparation procedures: a flow cytometry-based in vitro study. Stem Cells Int 2016:1764938, 8 pages. https://doi.org/10.1155/2016/1764938

    Article  PubMed  PubMed Central  Google Scholar 

  • Curfman G (2019) Stem cell therapy for heart failure: an unfulfilled promise? JAMA 321(12):1186–1187. https://doi.org/10.1001/jama.2019.2617

    Article  PubMed  Google Scholar 

  • Dimmeler S, Leri A (2008) Aging and disease as modifiers of efficacy of cell therapy. Circ Res 102(11):1319–1330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukuda K, Fujita J (2005) Mesenchymal, but not hematopoietic, stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction in mice. Kidney Int 68:1940–1943

    Article  CAS  PubMed  Google Scholar 

  • Furlani D, Li W, Pittermann E, Klopsch C, Wang L, Knopp A, Jungebluth P et al (2009) A transformed cell population derived from cultured mesenchymal stem cells has no functional effect after transplantation into the injured heart. Cell Transplant 18(3):319–332

    Article  PubMed  Google Scholar 

  • Gomez-Salazar M, Gonzalez-Galofre ZN, Casamitjana J, Crisan M, James AW, Péault B (2020) Five decades later, are mesenchymal stem cells still relevant? Front Bioeng Biotechnol 8:148. https://doi.org/10.3389/fbioe.2020.00148. PMID: 32185170; PMCID: PMC7058632

    Article  PubMed  PubMed Central  Google Scholar 

  • Haider KH (2017) Hematopoietic stem cell transplantation: the quality matters. J Stem Cell Res Ther 7:6

    Article  Google Scholar 

  • Haider KH (2018) Bone marrow cell therapy and cardiac reparability: better cell characterization will enhance clinical success. Regen Med 13(4):457–475. https://doi.org/10.2217/rme-2017-0134

    Article  CAS  PubMed  Google Scholar 

  • Haider KH, Jiang S, Niagara MI, Ashraf M (2008) IGF-I over expressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1α/CXCR4 signaling to promote myocardial repair. Circ Res 103:1300–1308. https://doi.org/10.1161/CIRCRESAHA.108.186742

    Article  CAS  PubMed  Google Scholar 

  • Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M et al (2012) Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA 308(22):2369–2379. https://doi.org/10.1001/jama.2012.25321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hare JM, DiFede DL, Rieger AC, Florea V, Landin AM, El-Khorazaty J, Khan A et al (2017) Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM trial. J Am Coll Cardiol 69(5):526–537. https://doi.org/10.1016/j.jacc.2016.11.009

    Article  PubMed  Google Scholar 

  • Hoch AI, Leach JK (2014) Concise review: optimizing expansion of bone marrow mesenchymal stem/stromal cells for clinical applications. Stem Cells Transl Med 3(5):643–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L et al (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. PNAS 99(13):8932–8937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ (2005) International Society for Cellular Therapy. Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy 7(5):393–395. https://doi.org/10.1080/14653240500319234

    Article  CAS  PubMed  Google Scholar 

  • Jansen of Lorkeers SJ, JEC E, Vesterinen HM, van der Spoel TIG, Sena ES, Duckers HJ, Doevendas PA et al (2015) Similar effect of autologous and allogeneic cell therapy for ischemic heart disease: systematic review and meta-analysis of large animal studies. Circ Res 116:80–86. https://doi.org/10.1161/CIRCRESAHA.116.304872

    Article  CAS  PubMed  Google Scholar 

  • Jeger-Madiot N, Arakelian L, Setterblad N, Bruneval P, Hoyos M, Larghero J, Aider JL (2021) Self-organization and culture of mesenchymal stem cell spheroids in acoustic levitation. Sci Rep 11:8355. https://doi.org/10.1038/s41598-021-87459-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang S, Haider KH, Niagara MI, Salim A, Ashraf M (2006) Supportive interaction between cell survival signaling and angio-competent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair. Circ Res 99:776–784. https://doi.org/10.1161/01.RES.0000244687.97719.4f

    Article  CAS  PubMed  Google Scholar 

  • Jiang S, Haider KH, Rafeeq PHA, Niagara MI, Salim A, Ashraf M (2008) Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium. J Mol Cell Cardiol 44(3):582–596

    Article  CAS  PubMed  Google Scholar 

  • Jiang T, Xu G, Wang Q, Yang L, Zheng L, Zhao J, Zhang X et al (2017) In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects. Cell Death Dis 8:e2851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaplan A, Sackett K, Sumstad D, Kadidlo D, McKenna DH (2017) Impact of starting material (fresh versus cryopreserved marrow) on mesenchymal stem cell culture. Transfusion. https://doi.org/10.1111/trf.14192

  • Karantalis V, Schulman IH, Balkan W, Hare JM (2016) Allogeneic cell therapy: a new paradigm in therapeutics. Circ Res 116(1):12–15. https://doi.org/10.1161/CIRCRESAHA.114.305495

    Article  CAS  Google Scholar 

  • Kariminekoo S, Movassaghpour A, Rahimzadeh A, Talebi M, Shamsasenjan K, Akbarzadeh A (2016) Implications of mesenchymal stem cells in regenerative medicine. Artif Cells Nanomed Biotechnol 44(3):749–757. https://doi.org/10.3109/21691401.2015.1129620

    Article  CAS  PubMed  Google Scholar 

  • Khan M, Mohsin S, Khan SN, Riazuddin S (2011) Repair of senescent myocardium by mesenchymal stem cells is dependent on the age of donor mice. J Cell Mol Med 15(7):1515–1527. https://doi.org/10.1111/j.1582-4934.2009.00998.x

    Article  CAS  PubMed  Google Scholar 

  • Kinkaid HYM, Huang X-P, Li R-K, Weisel RD (2010) What’s new in cardiac cell therapy? Allogeneic bone marrow stromal cells as “universal donor cells”. J Card Surg 25:359–366. https://doi.org/10.1111/j.1540-8191.2009.00984.x

    Article  PubMed  Google Scholar 

  • Kissel CK, Lehmann R, Assmus B, Aicher A, Honold J, Fischer-Rasokat U, Heeschen C et al (2007) Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure. J Am Coll Cardiol 49(24):2341–2349

    Article  PubMed  Google Scholar 

  • Koç ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, Lazarus HM (2000) Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 18(2):307–316. https://doi.org/10.1200/JCO.2000.18.2.307

    Article  PubMed  Google Scholar 

  • Koç ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W (2002) Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 30(4):215–222

    Google Scholar 

  • Koh SH, Baik W, Noh MY, Cho GW, Kim HY, Kim KS, Kim SH (2012) The functional deficiency of bone marrow mesenchymal stromal cells in ALS patients is proportional to disease progression rate. Exp Neurol 233(1):472–480. https://doi.org/10.1016/j.expneurol.2011.11.021

    Article  CAS  PubMed  Google Scholar 

  • Koichi I, Haider KH, Ahmed RPH, Sheriff S, Ashraf M (2011) Neuropeptide-Y (NPY) and NPY Y5 receptor (Y5R) interaction restores impaired growth potential of ageing bone marrow stromal cells. Rejuvenation Res 14(4):393–403

    Article  Google Scholar 

  • Kowal JM, Möller S, Ali D, Figeac F, Barington T, Schmal H, Kassem M (2021) Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells. Stem Cell Res Ther 12(1):265. https://doi.org/10.1186/s13287-021-02338-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kucerova L, Altanerova V, Matuskova M, Tyciakova S, Altaner C (2007) Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy. Cancer Res 67(13):6304–6313. https://doi.org/10.1158/0008-5472.CAN-06-4024

    Article  CAS  PubMed  Google Scholar 

  • Lakota J (2014a) Dubrovcakova M, Bohovic R, Goncalvesova E. Intracoronary mesenchymal stem cell transplantation in patients with ischemic cardiomyopathy. Int J Cardiol 176(2):547–549. https://doi.org/10.1016/j.ijcard.2014.07.024

    Article  PubMed  Google Scholar 

  • Lakota J (2014b) The healing of Ulcus Cruris by mesenchymal stem cells: no delay in wound healing by high-dose and standard chemotherapy. Int J Hematol Oncol Stem Cell Res 8(3):58–59. PMID: 25642310; PMCID: PMC4305383

    PubMed  PubMed Central  Google Scholar 

  • Lakota J (2016) Molecular mechanism of ischemia-reperfusion injury after myocardial infarction and its possible targeted treatment. Int J Cardiol 220:571–572. https://doi.org/10.1016/j.ijcard.2016.06.309

    Article  PubMed  Google Scholar 

  • Lakota J (2017a) The use of donor mesenchymal stem cells in the treatment of steroid refractory graft versus host disease. Ten years of single center experience. Ann Hematol Oncol 4(5):1152. ISSN:2375-7965

    Google Scholar 

  • Lakota J (2017b) Onkológia (Bratisl.), 2017; roč. 12(5): 376. (in Slovak)

    Google Scholar 

  • Lakota J (2018) Fate of human mesenchymal stem cells (MSCs) in humans and rodents-is the current paradigm obtained on rodents applicable to humans? J Cell Mol Med 22(4):2523–2524. https://doi.org/10.1111/jcmm.13561

    Article  PubMed  PubMed Central  Google Scholar 

  • Lakota J, Gocarova K, Spanik S (2015) Treatment of metastatic head and neck cancer with mesenchymal stem cells combined with prodrug gene therapy. Exp Oncol 37(4):298

    Article  CAS  PubMed  Google Scholar 

  • Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Canadian Critical Care Trials Group et al (2012) Safety of cell therapy with mesenchymal stromal cells (safecell): a systematic review and meta-analysis of clinical trials. PLoS One 7(10):e47559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363(9419):1439–1441. https://doi.org/10.1016/S0140-6736(04)16104-7

    Article  PubMed  Google Scholar 

  • Liu Y, Li Z, Liu T, Xue X, Jiang H, Huang J, Wang H (2013) Impaired cardioprotective function of transplantation of mesenchymal stem cells from patients with diabetes mellitus to rats with experimentally induced myocardial infarction. Cardiovasc Diabetol 12(1):1–0

    Article  Google Scholar 

  • Lohan P, Coleman CM, Murphy JM, Griffin MD, Ritter T, Ryan AE (2014) Changes in immunological profile of allogeneic mesenchymal stem cells after differentiation: should we be concerned? Stem Cell Res Ther 5(4):99

    Article  PubMed  PubMed Central  Google Scholar 

  • Machado C d V, Telles PD, Nascimento IL (2013) Immunological characteristics of mesenchymal stem cells. Rev Bras Hematol Hemoter 35(1):62–67. https://doi.org/10.5581/1516-8484.20130017. PMID: 23580887; PMCID: PMC3621638

    Article  PubMed  PubMed Central  Google Scholar 

  • Maijenburg MW, Kleijer M, Vermeul K, Mul EP, van Alphen FP, van der Schoot CE, Voermans C (2012) The composition of the mesenchymal stromal cell compartment in human bone marrow changes during development and aging. Haematologica 97(2):179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malik NN, Durdy MB (2015) Cell therapy landscape: autologous and allogeneic approaches, Chapter 7. In: Atala A, Allickson JG (eds) Translational regenerative medicine. Academic, pp 87–106. https://doi.org/10.1016/B978-0-12-410396-2.00007-4. ISBN 9780124103962

    Chapter  Google Scholar 

  • Mamidi MK, Nathan KG, Singh G et al (2012) Comparative cellular and molecular analyses of pooled bone marrow multipotent mesenchymal stromal cells during continuous passaging and after successive cryopreservation. J Cell Biochem 113(10):3153–3164

    Article  CAS  PubMed  Google Scholar 

  • Marshall D, Sharpe M, Ward S (2016) Cell & gene therapies and the evolving role of personalized medicine. Cell Gene Ther Insights 2(2):277–286. https://doi.org/10.18609/cgti.2016.034

    Article  Google Scholar 

  • Masic I, Miokovic M, Muhamedagic B (2008) Evidence based medicine – new approaches and challenges. Acta Inform Med 16(4):219–225. https://doi.org/10.5455/aim.2008.16.219-225

    Article  PubMed  PubMed Central  Google Scholar 

  • Musiał-Wysocka A, Kot M, Majka M (2019) The pros and cons of mesenchymal stem cell-based therapies. Cell Transplant 28(7):801–812. https://doi.org/10.1177/0963689719837897

    Article  PubMed  PubMed Central  Google Scholar 

  • Oh J, Lee YD, Wagers AJ (2014) Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat Med 20(8):870–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orlic D, Kajstura J, Chimenti S et al (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410(6829):701–705

    Article  CAS  PubMed  Google Scholar 

  • Pachon-Pena G, Serena C, Ejarque M, Petriz J, Duran X, Oliva-Olivera W, Simo R (2016) Obesity determines the immunophenotypic profile and functional characteristics of human mesenchymal stem cells from adipose tissue. Stem Cells Transl Med 5:464–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pawitan JA, Bui TA, Mubarok W, Antarianto RD, Nurhayati RW, Dilogo IH, Oceandy D (2020) Enhancement of the therapeutic capacity of mesenchymal stem cells by genetic modification: a systematic review. Front Cell Dev Biol 8:587776. https://doi.org/10.3389/fcell.2020.587776

    Article  PubMed  PubMed Central  Google Scholar 

  • Pérez LM, de Lucas B, Gálvez BG (2018) Unhealthy stem cells: when health conditions upset stem cell properties. Cell Physiol Biochem 46:1999–2016. https://doi.org/10.1159/000489440

    Article  CAS  PubMed  Google Scholar 

  • Poh KK, Sperry E, Young RG, Freyman T, Barringhaus KG, Thompson CA (2007) Repeated direct endomyocardial transplantation of allogeneic mesenchymal stem cells: safety of a high dose, “off-the-shelf”, cellular cardiomyoplasty strategy. Int J Cardiol 117(3):360–364

    Article  PubMed  Google Scholar 

  • Quevedoa HC, Hatzistergosa KE, Oskoueia BN et al (2009) Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. PNAS 106(33):14022–14027

    Article  Google Scholar 

  • Rady D, Abbass MMS, El-Rashidy AA, El Moshy S, Radwan IA, Dörfer CE, Fawzy El-Sayed KM (2020) Mesenchymal stem/progenitor cells: the prospect of human clinical translation. Stem Cells Int 2020:8837654. https://doi.org/10.1155/2020/8837654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Røsland GV, Svendsen A, Torsvik A et al (2009) Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res 69(13):5331–5339

    Article  PubMed  Google Scholar 

  • Sawchik J, Hamdani J, Vanhaeverbeek M (2018) Randomized clinical trials and observational studies in the assessment of drug safety. Rev Epidemiol Sante Publique 66(3):217–225. https://doi.org/10.1016/j.respe.2018.03.133

    Article  CAS  PubMed  Google Scholar 

  • Schultz MB, Sinclair DA (2016) When stem cells grow old: phenotypes and mechanisms of stem cell aging. Development 143(1):3–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shahid MS, Lasheen W, Haider KH (2016) Modest outcome of clinical trials with bone marrow cells for myocardial repair: is the autologous source of cells the prime culprit? J Thorac Dis 8(10):E1371–E1374

    Article  PubMed  PubMed Central  Google Scholar 

  • Shen C, Jiang T, Zhu B, Le Y, Liu J, Qin Z, Chen H et al (2018) In vitro culture expansion impairs chondrogenic differentiation and the therapeutic effect of mesenchymal stem cells by regulating the unfolded protein response. J Biol Eng 12(1):1–2

    Article  Google Scholar 

  • Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33(6):919–926. https://doi.org/10.1016/j.bone.2003.07.005

    Article  PubMed  Google Scholar 

  • Stolzinga A, Jonesb T, McGonagleb D, Scutta A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129(3):163–173

    Article  Google Scholar 

  • Tan YZ, Xu XY, Dai JM, Yin Y, He X-T, Zhang Y-L, Zhu T-X et al (2021) Melatonin induces the rejuvenation of long-term ex vivo expanded periodontal ligament stem cells by modulating the autophagic process. Stem Cell Res Ther 12:254. https://doi.org/10.1186/s13287-021-02322-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD (2004) Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363(9411):783–784. https://doi.org/10.1016/S0140-6736(04)15695-X

    Article  PubMed  Google Scholar 

  • Wolf D, Reinhard A, Wolf D, Reinhard A, Seckinger A, Gross L (2009) Regenerative capacity of intravenous autologous, allogeneic and human mesenchymal stem cells in the infarcted pig myocardium – complicated by myocardial tumor formation. Scand Cardiovasc J 43(1):39–45

    Article  CAS  PubMed  Google Scholar 

  • Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, Acker MA, Cardiothoracic Surgical Trials Network et al (2019) Intramyocardial injection of mesenchymal precursor cells and successful temporary weaning from left ventricular assist device support in patients with advanced heart failure: a randomized clinical trial. JAMA 321(12):1176–1186. https://doi.org/10.1001/jama.2019.2341

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Huang X, Wang H, Liu X, Zhang T, Yunchuan W, Hu D (2015) The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy. Stem Cell Res Ther 6. https://doi.org/10.1186/s13287-015-0240-9

  • Zhou S, Greenberger JS, Epperly MW et al (2008) Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell 7(3):335–343

    Article  CAS  PubMed  Google Scholar 

  • Zhuo Y, Li SH, Chen MS, Wu J, Kinkaid HY, Fazel S, Weisel RD, Li RK (2010) Aging impairs the angiogenic response to ischemic injury and the activity of implanted cells: combined consequences for cell therapy in older recipients. J Thorac Cardiovasc Surg 139(5):1286–1294

    Article  PubMed  Google Scholar 

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Lakota, J., Dubrovcakova, M., Haider, K.H. (2022). Human Mesenchymal Stem Cells: The Art to Use Them in the Treatment of Previously Untreatable. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-19-2655-6_1

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