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DOI: 10.1055/a-0610-9685
Mesenchymale Stromazellen auf dem Weg zur klinischen Anwendung: Update 2018
Mesenchymal Stromal Cells on Their Way from Bench to Bedside: Update 2018Publikationsverlauf
Publikationsdatum:
21. August 2018 (online)
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Zusammenfassung
Mesenchymale Stromazellen (MSC) besitzen ein großes therapeutisches Potenzial sowohl für Immunmodulation als auch regenerative Therapie. In einigen Indikationen, z. B. Behandlung der schweren Transplantat-gegen-Empfänger-Reaktion nach allogener Stammzelltransplantation, wurden MSC schon vor mehr als 10 Jahren therapeutisch eingesetzt. In weiteren Indikationen haben die MSC in den letzten Jahren nun das Stadium der klinischen Erprobung erreicht. Hier erfolgt eine Evaluation der Sicherheit und Wirksamkeit einer MSC-Therapie in einem sehr breiten Spektrum von Erkrankungen. Diese Übersichtsarbeit stellt den aktuellen Stand der präklinischen und klinischen Forschung zur Anwendung von MSC in der Behandlung der Transplantat-gegen-Empfänger-Reaktion, von Wundheilungsstörungen, von neurodegenerativen Erkrankungen und Knochen- und Knorpeldefekten dar.
Abstract
Mesenchymal stromal cells (MSC) show a high therapeutic potential in immunomudulation as well as in regenerative medicine. For some indications, e.g. treatment of severe graft-versus-host-disease following allogenic stem cell transplantation, MSC have already been tested for more than 10 years. For other indications, clinical application of MSC is under investigation to evaluate safety and efficacy of MSC treatment in a broad spectrum of diseases. This review presents recent pre-clinical and clinical research data on MSC on the treatment of graft-versus-host-disease, wound healing, neurodegenerative disorders and defects of bone and joint.
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Literatur
- 1 Crisan M, Yap S, Casteilla L. et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 2008; 3: 301-313
- 2 Börger V, Görgens A, Rhode E. et al. Therapeutisches Potenzial von extrazellulären Vesikeln aus mesenchymalen Stamm- bzw. Stromazellen. Transfusionsmedizin 2015; 5: 131-137
- 3 Fekete N, Rojewski MT, Furst D. et al. GMP-compliant isolation and large-scale expansion of bone marrow-derived MSC. PLoS One 2012; 7: e43255
- 4 Rojewski MT, Fekete N, Baila S. et al. GMP-compliant isolation and expansion of bone marrow-derived MSCs in the closed, automated device quantum cell expansion system. Cell Transplant 2013; 22: 1981-2000
- 5 Fekete N, Gadelorge M, Furst D. et al. Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components. Cytotherapy 2012; 14: 540-554
- 6 Fekete N, Rojewski MT, Lotfi R. et al. Essential components for ex vivo proliferation of mesenchymal stromal cells. Tissue Eng Part C Methods 2014; 20: 129-139
- 7 Bieback K, Hecker A, Kocaomer A. et al. Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells 2009; 27: 2331-2341
- 8 Dominici M, Le Blanc K, Mueller I. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317
- 9 Deeg HJ. How I treat refractory acute GVHD. Blood 2007; 109: 4119-4126
- 10 Hashmi S, Ahmed M, Murad MH. et al. Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft-versus-host disease: systematic review and meta-analysis. Lancet Haematol 2016; 3: e45-e52
- 11 Martin PJ, Rizzo JD, Wingard JR. et al. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2012; 18: 1150-1163
- 12 Le Blanc K, Rasmusson I, Sundberg B. et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363: 1439-1441
- 13 Ringden O, Uzunel M, Rasmusson I. et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 2006; 81: 1390-1397
- 14 Le Blanc K, Frassoni F, Ball L. et al. Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008; 371: 1579-1586
- 15 Ball LM, Bernardo ME, Roelofs H. et al. Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade III–IV acute graft-versus-host disease. Br J Haematol 2013; 163: 501-509
- 16 Lucchini G, Introna M, Dander E. et al. Platelet-lysate-expanded mesenchymal stromal cells as a salvage therapy for severe resistant graft-versus-host disease in a pediatric population. Biol Blood Marrow Transplant 2010; 16: 1293-1301
- 17 Muller I, Kordowich S, Holzwarth C. et al. Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis 2008; 40: 25-32
- 18 Resnick IB, Barkats C, Shapira MY. et al. Treatment of severe steroid resistant acute GVHD with mesenchymal stromal cells (MSC). Am J Blood Res 2013; 3: 225-238
- 19 Chen X, Wang C, Yin J. et al. Efficacy of mesenchymal stem cell therapy for steroid-refractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. PLoS One 2015; 10: e0136991
- 20 von Bahr L, Sundberg B, Lonnies L. et al. Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant 2012; 18: 557-564
- 21 Kuci Z, Bonig H, Kreyenberg H. et al. Mesenchymal stromal cells from pooled mononuclear cells of multiple bone marrow donors as rescue therapy in pediatric severe steroid-refractory graft-versus-host disease: a multicenter survey. Haematologica 2016; 101: 985-994
- 22 Bader P, Kuci Z, Bakhtiar S. et al. Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM). Bone Marrow Transplant 2018; DOI: 10.1038/s41409-018-0102-z.
- 23 Kurtzberg J, Prockop S, Teira P. et al. Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients. Biol Blood Marrow Transplant 2014; 20: 229-235
- 24 Australian Government, Department of Health, Therapeutic Goods Administration. Australian Public Assessment Report for Remestemcel-L, ex vivo adult human mesenchymal stem cells. 03/2015 Im Internet: https://www.tga.gov.au/sites/default/files/auspar-remestemcel-l-150315.pdf Stand: 02.07.2018
- 25 Martin PJ, Uberti JP, Soiffer RJ. et al. Prochymal improves response rates in patients with steroid-refractory acute graft versus host disease (SR-GVHD) involving the liver and gut: results of a randomized, placebo-controlled, multicenter phase III trial In GVHD. Biol Blood Marrow Transplant 2010; 16: S169-S170
- 26 Introna M, Lucchini G, Dander E. et al. Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients. Biol Blood Marrow Transplant 2014; 20: 375-381
- 27 Prasad VK, Lucas KG, Kleiner GI. et al. Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study. Biol Blood Marrow Transplant 2011; 17: 534-541
- 28 Salmenniemi U, Itala-Remes M, Nystedt J. et al. Good responses but high TRM in adult patients after MSC therapy for GvHD. Bone Marrow Transplant 2017; 52: 606-608
- 29 Dotoli GM, De Santis GC, Orellana MD. et al. Mesenchymal stromal cell infusion to treat steroid-refractory acute GvHD III/IV after hematopoietic stem cell transplantation. Bone Marrow Transplant 2017; 52: 859-862
- 30 von Dalowski F, Kramer M, Wermke M. et al. Mesenchymal stromal cells for treatment of acute steroid-refractory graft versus host disease: clinical responses and long-term outcome. Stem Cells 2016; 34: 357-366
- 31 Diener H, Kleinspehn E, Larena-Avellaneda A. et al. Wundheilungsstörungen im Kontext – Epidemiologie und Pathophysiologie. Gefäßchirurgie 2017; 22: 524-532
- 32 Martin P. Wound healing – aiming for perfect skin regeneration. Science 1997; 276: 75-81
- 33 Badiavas EV, Abedi M, Butmarc J. et al. Participation of bone marrow derived cells in cutaneous wound healing. J Cell Physiol 2003; 196: 245-250
- 34 Dash SN, Dash NR, Guru B. et al. Towards reaching the target: clinical application of mesenchymal stem cells for diabetic foot ulcers. Rejuvenation Res 2014; 17: 40-53
- 35 Jackson WM, Nesti LJ, Tuan RS. Concise review: clinical translation of wound healing therapies based on mesenchymal stem cells. Stem Cells Transl Med 2012; 1: 44-50
- 36 Mulder GD, Lee DK, Jeppesen NS. Comprehensive review of the clinical application of autologous mesenchymal stem cells in the treatment of chronic wounds and diabetic bone healing. Int Wound J 2012; 9: 595-600
- 37 Otero-Vinas M, Falanga V. Mesenchymal stem cells in chronic wounds: the spectrum from basic to advanced therapy. Adv Wound Care (New Rochelle) 2016; 5: 149-163
- 38 Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 2015; 17: 11-22
- 39 Fontaine MJ, Shih H, Schafer R. et al. Unraveling the mesenchymal stromal cellsʼ paracrine immunomodulatory effects. Transfus Med Rev 2016; 30: 37-43
- 40 Ennis WJ, Sui A, Bartholomew A. Stem cells and healing: impact on inflammation. Adv Wound Care (New Rochelle) 2013; 2: 369-378
- 41 Regulski MJ. Mesenchymal stem cells: “Guardians of Inflammation”. Wounds 2017; 29: 20-27
- 42 Moll G, Ignatowicz L, Catar R. et al. Different procoagulant sctivity of therapeutic mesenchymal stromal cells derived from bone marrow and placental decidua. Stem Cells Dev 2015; 24: 2269-2279
- 43 Oeller M, Laner-Plamberger S, Hochmann S. et al. Selection of tissue factor-deficient cell transplants as a novel strategy for improving hemocompatibility of human bone marrow stromal cells. Theranostics 2018; 8: 1421-1434
- 44 Siegel G, Schafer R, Dazzi F. The immunosuppressive properties of mesenchymal stem cells. Transplantation 2009; 87: S45-S49
- 45 Mattar P, Bieback K. Comparing the immunomodulatory properties of bone marrow, adipose tissue, and birth-associated tissue mesenchymal stromal cells. Front Immunol 2015; 6: 560
- 46 Menard C, Pacelli L, Bassi G. et al. Clinical-grade mesenchymal stromal cells produced under various good manufacturing practice processes differ in their immunomodulatory properties: standardization of immune quality controls. Stem Cells Dev 2013; 22: 1789-1801
- 47 Qi Y, Jiang D, Sindrilaru A. et al. TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds. J Invest Dermatol 2014; 134: 526-537
- 48 Basu A, Munir S, Mulaw MA. et al. A novel S100A8/A9 induced fingerprint of mesenchymal stem cells associated with enhanced wound healing. Sci Rep 2018; 8: 6205
- 49 Sanchez-Munoz I, Granados R, Holguin Holgado P. et al. The use of adipose mesenchymal stem cells and human umbilical vascular endothelial cells on a fibrin matrix for endothelialized skin substitute. Tissue Eng Part A 2015; 21: 214-223
- 50 Sukpat S, Isarasena N, Wongphoom J. et al. Vasculoprotective effects of combined endothelial progenitor cells and mesenchymal stem cells in diabetic wound care: their potential role in decreasing wound-oxidative stress. Biomed Res Int 2013; 2013: 459196
- 51 Lee SH, Jin SY, Song JS. et al. Paracrine effects of adipose-derived stem cells on keratinocytes and dermal fibroblasts. Ann Dermatol 2012; 24: 136-143
- 52 Rodriguez-Menocal L, Salgado M, Ford D. et al. Stimulation of skin and wound fibroblast migration by mesenchymal stem cells derived from normal donors and chronic wound patients. Stem Cells Transl Med 2012; 1: 221-229
- 53 Hanson SE. Mesenchymal stem cells: a multimodality option for wound healing. Adv Wound Care (New Rochelle) 2012; 1: 153-158
- 54 Li Z, Han S, Wang X. et al. Rho kinase inhibitor Y-27632 promotes the differentiation of human bone marrow mesenchymal stem cells into keratinocyte-like cells in xeno-free conditioned medium. Stem Cell Res Ther 2015; 6: 17
- 55 Sundaramurthi D, Krishnan UM, Sethuraman S. Epidermal differentiation of stem cells on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers. Ann Biomed Eng 2014; 42: 2589-2599
- 56 Harman RM, Yang S, He MK. et al. Antimicrobial peptides secreted by equine mesenchymal stromal cells inhibit the growth of bacteria commonly found in skin wounds. Stem Cell Res Ther 2017; 8: 157
- 57 Meisel R, Brockers S, Heseler K. et al. Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase. Leukemia 2011; 25: 648-654
- 58 Falanga V, Iwamoto S, Chartier M. et al. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Eng 2007; 13: 1299-1312
- 59 Yufit T, Carson P, Falanga V. Topical delivery of cultured stem cells to human non-healing wounds: GMP facility development in an academic setting and FDA requirements for an IND and human testing. Curr Drug Deliv 2014; 11: 572-581
- 60 Ringburg AN, Polinder S, van Ierland MC. et al. Prevalence and prognostic factors of disability after major trauma. J Trauma 2011; 70: 916-922
- 61 Friedlaender GE, Perry CR, Cole JD. et al. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 2001; 83-A (Suppl. 01) S151-S158
- 62 Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71-74
- 63 Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970; 3: 393-403
- 64 Pittenger MF, Mackay AM, Beck SC. et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147
- 65 Jaiswal N, Haynesworth SE, Caplan AI. et al. Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 1997; 64: 295-312
- 66 Bruder SP, Ricalton NS, Boynton RE. et al. Mesenchymal stem cell surface antigen SB-10 corresponds to activated leukocyte cell adhesion molecule and is involved in osteogenic differentiation. J Bone Miner Res 1998; 13: 655-663
- 67 Brennan MA, Renaud A, Amiaud J. et al. Pre-clinical studies of bone regeneration with human bone marrow stromal cells and biphasic calcium phosphate. Stem Cell Res Ther 2014; 5: 114
- 68 Brennan MA, Renaud A, Guilloton F. et al. Inferior in vivo osteogenesis and superior angiogeneis of human adipose tissue: a comparison with bone marrow-derived stromal stem cells cultured in xeno-free conditions. Stem Cells Transl Med 2017; 6: 2160-2172
- 69 Dumanian ZP, Tollemar V, Ye J. et al. Repair of critical sized cranial defects with BMP9-transduced calvarial cells delivered in a thermoresponsive scaffold. PLoS One 2017; 12: e0172327
- 70 Gamblin AL, Brennan MA, Renaud A. et al. Bone tissue formation with human mesenchymal stem cells and biphasic calcium phosphate ceramics: the local implication of osteoclasts and macrophages. Biomaterials 2014; 35: 9660-9667
- 71 Gomez-Barrena E, Rosset P, Gebhard F. et al. Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial. Biomaterials 2018; DOI: 10.1016/j.biomaterials.2018.03.033.
- 72 Veronesi E, Murgia A, Caselli A. et al. Transportation conditions for prompt use of ex vivo expanded and freshly harvested clinical-grade bone marrow mesenchymal stromal/stem cells for bone regeneration. Tissue Eng Part C Methods 2014; 20: 239-251
- 73 Castillo-Cardiel G, Lopez-Echaury AC, Saucedo-Ortiz JA. et al. Bone regeneration in mandibular fractures after the application of autologous mesenchymal stem cells, a randomized clinical trial. Dent Traumatol 2017; 33: 38-44
- 74 Al-Najar M, Khalil H, Al-Ajlouni J. et al. Intra-articular injection of expanded autologous bone marrow mesenchymal cells in moderate and severe knee osteoarthritis is safe: a phase I/II study. J Orthop Surg Res 2017; 12: 190
- 75 Pers YM, Rackwitz L, Ferreira R. et al. Adipose mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Transl Med 2016; 5: 847-856
- 76 Shadmanfar S, Labibzadeh N, Emadedin M. et al. Intra-articular knee implantation of autologous bone marrow-derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial. Cytotherapy 2018; 20: 499-506
- 77 Chung R, Xian CJ. Recent research on the growth plate: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration. J Mol Endocrinol 2014; 53: T45-T61
- 78 Gomez-Barrena E, Padilla-Eguiluz NG, Avendano-Sola C. et al. A multicentric, open-label, randomized, comparative clinical trial of two different doses of expanded hBM-MSCs plus biomaterial versus iliac crest autograft, for bone healing in nonunions after long bone fractures: study protocol. Stem Cells Int 2018; 2018: 6025918
- 79 WHO. World Health Organization – Dementia Key Facts. 2017-12-12. Im Internet: http://www.who.int/news-room/fact-sheets/detail/dementia Stand: 22.06.2018
- 80 Giacobini E, Gold G. Alzheimer disease therapy – moving from amyloid-beta to tau. Nat Rev Neurol 2013; 9: 677-686
- 81 WHO. World Health Organization – Cardiovascular diseases (CVDs). 2017-05-17. Im Internet: http://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) Stand: 22.06.2018
- 82 SAFE. Stroke Alliance for Europe-The Stroke Patient Voice in EUROPE – How much does a stroke cost? SAFE is initiating a research project in 33 European countries. 2018-03-09. Im Internet: http://www.safestroke.eu/2018/03/09/how-much-does-a-stroke-cost-safe-is-initiating-a-research-project-in-33-european-countries/ Stand: 22.06.2018
- 83 Volkman R, Offen D. Concise review: mesenchymal stem cells in neurodegenerative diseases. Stem Cells 2017; 35: 1867-1880
- 84 Heneka MT, Carson MJ, El Khoury J. et al. Neuroinflammation in Alzheimerʼs disease. Lancet Neurol 2015; 14: 388-405
- 85 Walker LC, Jucker M. Amyloid by default. Nat Neurosci 2011; 14: 669-670
- 86 Rennert RC, Schafer R, Bliss T. et al. High-resolution microfluidic single-cell transcriptional profiling reveals clinically relevant subtypes among human stem cell populations commonly utilized in cell-based therapies. Front Neurol 2016; 7: 41
- 87 Schäfer R, Spohn G, Baer PC. Mesenchymal stem/stromal cells in regenerative medicine: Can preconditioning strategies improve therapeutic efficacy?. Transfus Med Hemother 2016; 43: 256-267
- 88 Neirinckx V, Coste C, Rogister B. et al. Concise review: adult mesenchymal stem cells, adult neural crest stem cells, and therapy of neurological pathologies: a state of play. Stem Cells Transl Med 2013; 2: 284-296
- 89 Danielyan L, Schafer R, Schulz A. et al. Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin. Cell Death Differ 2009; 16: 1599-1614
- 90 Fink KD, Deng P, Torrest A. et al. Developing stem cell therapies for juvenile and adult-onset Huntingtonʼs disease. Regen Med 2015; 10: 623-646
- 91 Karlupia N, Manley NC, Prasad K. et al. Intraarterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model. Stem Cell Res Ther 2014; 5: 45
- 92 Moon GJ, Cho YH, Kim DH. et al. Serum-mediated activation of bone marrow-derived mesenchymal stem cells in ischemic stroke patients: a novel preconditioning method. Cell Transplant 2018; 27: 485-500
- 93 Danielyan L, Schafer R, von Ameln-Mayerhofer A. et al. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease. Rejuvenation Res 2011; 14: 3-16
- 94 Danielyan L, Beer-Hammer S, Stolzing A. et al. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimerʼs and Parkinsonʼs disease. Cell Transplant 2014; 23 (Suppl. 01) S123-S139
- 95 Danielyan L, Schafer R, von Ameln-Mayerhofer A. et al. Intranasal delivery of cells to the brain. Eur J Cell Biol 2009; 88: 315-324
- 96 NIH, National Institute of Health, U.S. National Library of Medicine – ClinicalTrials.gov. The Long-Term Safety and Efficacy Follow-Up Study of Subjects Who Completed the Phase I Clinical Trial of Neurostem®-AD. 2018-06-22. Im Internet: https://clinicaltrials.gov/ct2/show/NCT01696591?term=mesenchymal+stem+cells&cond=Alzheimer+Disease&rank=10 Stand: 22.06.2018
- 97 Kim HJ, Seo SW, Chang JW. et al. Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimerʼs disease dementia: A phase 1 clinical trial. Alzheimers Dement (N Y) 2015; 1: 95-102
- 98 NIH, National Institute of Health, U.S. National Library of medicine – ClinicalTrials.gov. Studies found for: “Parkinson Disease”. 2018-06-22. Im Internet: https://clinicaltrials.gov/ct2/results?cond=Parkinson+Disease&term=mesenchymal+stem+cells&cntry=&state=&city=&dist Stand: 22.06.2018
- 99 NIH, National Institute of Health, U.S. National Library of medicine – ClinicalTrials.gov. Studies found for: “Huntington Disease”. 2018-06-22. Im Internet: https://clinicaltrials.gov/ct2/results?cond=Huntington+Disease&term=mesenchymal+stem+cells&cntry=&state=&city=&dist= Stand: 22.06.2018
- 100 Canesi M, Giordano R, Lazzari L. et al. Finding a new therapeutic approach for no-option Parkinsonisms: mesenchymal stromal cells for progressive supranuclear palsy. J Transl Med 2016; 14: 127
- 101 Venkataramana NK, Kumar SK, Balaraju S. et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinsonʼs disease. Transl Res 2010; 155: 62-70
- 102 NIH, National Institute of Health, U.S. National Library of medicine – ClinicalTrials.gov. Studies found for: “mesenchymal stromal cells” and “ALS (Amyotrophic Lateral Sclerosis)”. 2018-06-22. Im Internet: https://clinicaltrials.gov/ct2/results?cond=ALS+%2528Amyotrophic+Lateral+Sclerosis%2529&term=mesenchymal+stem+cells&cntry=&state=&city=&dist= Stand: 22.06.2018
- 103 NIH, National Institute of Health, U.S. National Library of medicine – ClinicalTrials.gov. Studies found for: “mesenchymal stem” and “Stroke”. 2018-06-22. Im Internet: https://clinicaltrials.gov/ct2/results?cond=Stroke&term=mesenchymal+stem+cells&cntry=&state&city=&dist= Stand: 22.06.2018
- 104 Petrou P, Gothelf Y, Argov Z. et al. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA Neurol 2016; 73: 337-344
- 105 Steinberg GK, Kondziolka D, Wechsler LR. et al. Clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: a phase 1/2a study. Stroke 2016; 47: 1817-1824
- 106 Cohn Yakubovich D, Sheyn D, Bez M. et al. Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures. Stem Cell Res Ther 2017; 8: 51
- 107 Lebouvier A, Poignard A, Cavet M. et al. Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection. Stem Cell Res Ther 2015; 6: 68
- 108 Otsuru S, Desbourdes L, Guess AJ. et al. Extracellular vesicles released from mesenchymal stromal cells stimulate bone growth in osteogenesis imperfecta. Cytotherapy 2018; 20: 62-73
- 109 Lee K, Park N, Jung H. et al. Mesenchymal stem cells ameliorate experimental arthritis via expression of interleukin-1 receptor antagonist. PLoS One 2018; 13: e0193086
- 110 Desando G, Cavallo C, Sartoni F. et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther 2013; 15: R22
- 111 Gotherstrom C, Westgren M, Shaw SW. et al. Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience. Stem Cells Transl Med 2014; 3: 255-264