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Injectable Allogenic Mesenchymal Stromal Cells: Advantages, Disadvantages, and Challenges

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Orthobiologics

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Abstract

Culture expansion of adult mesenchymal stromal cells (MSCs) from mixed populations of tissue-specific connective tissue progenitors from bone marrow, perivascular cells, or adipose tissue has the potential to further our understanding of human physiology and may serve as a foundation for novel therapeutics in all areas of medicine. The use of allogeneic MSCs confers a number of theoretical benefits compared to alternative sourcing of MSCs. Specifically, allogeneic MSCs avoid the work, cost, and donor morbidity of harvesting cells directly from individual patients, may offer higher-quality cells compared to those available to the patient, and may confer immunologic benefits separate from tissue regeneration. However, there are drawbacks to the use of allogeneic MSCs, including immune response to foreign material and patient injury. Overall, the use of allogeneic MSCs is on the forefront of modern medicine and may represent a new method of therapy for the average patient; however, there is an acute need for future investigation to understand the risks, benefits, and limitations of allogeneic MSCs.

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References

  1. Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lo B, Parham L. Ethical issues in stem cell research. Endocr Rev. 2009;30(3):204–13.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Viswanathan S, Shi Y, Galipeau J, et al. Mesenchymal stem versus stromal cells: International Society for Cell & gene therapy (ISCT®) mesenchymal stromal cell committee position statement on nomenclature. Cytotherapy. 2019;21(10):1019–24.

    Article  CAS  PubMed  Google Scholar 

  4. Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Transl Med. 2017;6(6):1445–51.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Muschler GF, Midura RJ, Nakamoto C. Practical modeling concepts for connective tissue stem cell and progenitor compartment kinetics. J Biomed Biotechnol. 2003;2003(3):170–93.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Muschler GF, Midura RJ. Connective tissue progenitors: practical concepts for clinical applications. Clin Orthop Relat Res. 2002;395:66–80.

    Article  Google Scholar 

  7. Armitage JO. Bone marrow transplantation. N Engl J Med. 1994;330(12):827–38.

    Article  CAS  PubMed  Google Scholar 

  8. Hequet O. Hematopoietic stem and progenitor cell harvesting: technical advances and clinical utility. J Blood Med. 2015;6:55–67.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Korbling M, Freireich EJ. Twenty-five years of peripheral blood stem cell transplantation. Blood. 2011;117(24):6411–6.

    Article  CAS  PubMed  Google Scholar 

  10. Patterson TE, Boehm C, Nakamoto C, et al. The efficiency of bone marrow aspiration for the harvest of connective tissue progenitors from the human iliac crest. J Bone Joint Surg Am. 2017;99(19):1673–82.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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(4):315–7.

    Article  CAS  PubMed  Google Scholar 

  12. Strioga M, Viswanathan S, Darinskas A, Slaby O, Michalek J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev. 2012;21(14):2724–52.

    Article  CAS  PubMed  Google Scholar 

  13. Al-Nbaheen M, Vishnubalaji R, Ali D, et al. Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential. Stem Cell Rev Rep. 2013;9(1):32–43.

    Article  CAS  PubMed  Google Scholar 

  14. Ackermann J, Mestriner AB, Shah N, Gomoll AH. Effect of autogenous bone marrow aspirate treatment on magnetic resonance imaging integration of osteochondral allografts in the knee: a matched comparative imaging analysis. Arthroscopy. 2019;35(8):2436–44.

    Article  PubMed  Google Scholar 

  15. Wang D, Lin KM, Burge AJ, Balazs GC, Williams RJ. Bone marrow aspirate concentrate does not improve osseous integration of osteochondral allografts for the treatment of chondral defects in the knee at 6 and 12 months: a comparative magnetic resonance imaging analysis. Am J Sports Med. 2019;47(2):339–46.

    Article  PubMed  Google Scholar 

  16. Stoker AM, Baumann CA, Stannard JP, Cook JL. Bone marrow aspirate concentrate versus platelet rich plasma to enhance osseous integration potential for osteochondral allografts. J Knee Surg. 2018;31(4):314–20.

    Article  PubMed  Google Scholar 

  17. Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am. 1997;79(11):1699–709.

    Article  CAS  PubMed  Google Scholar 

  18. Hyer CF, Berlet GC, Bussewitz BW, Hankins T, Ziegler HL, Philbin TM. Quantitative assessment of the yield of osteoblastic connective tissue progenitors in bone marrow aspirate from the iliac crest, tibia, and calcaneus. J Bone Joint Surg Am. 2013;95(14):1312–6.

    Article  PubMed  Google Scholar 

  19. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.

    Article  CAS  PubMed  Google Scholar 

  20. Veyrat-Masson R, Boiret-Dupré N, Rapatel C, et al. Mesenchymal content of fresh bone marrow: a proposed quality control method for cell therapy. Br J Haematol. 2007;139(2):312–20.

    Article  PubMed  Google Scholar 

  21. Hermann PC, Huber SL, Herrler T, et al. Concentration of bone marrow total nucleated cells by a point-of-care device provides a high yield and preserves their functional activity. Cell Transplant. 2008;16(10):1059–69.

    Article  PubMed  Google Scholar 

  22. Jager M, Herten M, Fochtmann U, et al. Bridging the gap: bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects. J Orthop Res. 2011;29(2):173–80.

    Article  PubMed  Google Scholar 

  23. Betsch M, Schneppendahl J, Thuns S, et al. Bone marrow aspiration concentrate and platelet rich plasma for osteochondral repair in a porcine osteochondral defect model. PLoS One. 2013;8(8):–e71602.

    Google Scholar 

  24. Hakimi M, Grassmann JP, Betsch M, et al. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting. PLoS One. 2014;9(6):e100143.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Liang X, Ding Y, Zhang Y, Tse H-F, Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant. 2014;23(9):1045–59.

    Article  PubMed  Google Scholar 

  26. Berglund AK, Fortier LA, Antczak DF, Schnabel LV. Immunoprivileged no more: measuring the immunogenicity of allogeneic adult mesenchymal stem cells. Stem Cell Res Ther. 2017;8(1):288.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Liechty KW, MacKenzie TC, Shaaban AF, et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med. 2000;6(11):1282–6.

    Article  CAS  PubMed  Google Scholar 

  28. Melick G, Hayman N, Landsman AS. Mesenchymal stem cell applications for joints in the foot and ankle. Clin Podiatr Med Surg. 2018;35(3):323–30.

    Article  PubMed  Google Scholar 

  29. Spaggiari GM, Capobianco A, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer–cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood. 2008;111(3):1327–33.

    Article  CAS  PubMed  Google Scholar 

  30. Jiang X-X, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105(10):4120–6.

    Article  CAS  PubMed  Google Scholar 

  31. Asari S, Itakura S, Ferreri K, et al. Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol. 2009;37(5):604–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Smith B, Sigal IR, Grande DA. Immunology and cartilage regeneration. Immunol Res. 2015;63(1):181–6.

    Article  CAS  PubMed  Google Scholar 

  33. Maumus M, Guérit D, Toupet K, Jorgensen C, Noël D. Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology. Stem Cell Res Ther. 2011;2(2):14.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Krampera M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 2003;101(9):3722–9.

    Article  CAS  PubMed  Google Scholar 

  35. Nasef A, Mathieu N, Chapel A, et al. Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation. 2007;84(2):231–7.

    Article  CAS  PubMed  Google Scholar 

  36. Borger V, Bremer M, Ferrer-Tur R, et al. Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents. Int J Mol Sci. 2017;18:7.

    Article  CAS  Google Scholar 

  37. Yu B, Zhang X, Li X. Exosomes derived from mesenchymal stem cells. Int J Mol Sci. 2014;15(3):4142–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lamo-Espinosa JM, Mora G, Blanco JF, et al. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2016;14(1):246.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Detante O, Moisan A, Dimastromatteo J, et al. Intravenous administration of 99mTc-HMPAO-Labeled human mesenchymal stem cells after stroke: in vivo imaging and biodistribution. Cell Transplant. 2009;18(12):1369–79.

    Article  PubMed  Google Scholar 

  40. Pigott JH, Ishihara A, Wellman ML, Russell DS, Bertone AL. Investigation of the immune response to autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses. Vet Immunol Immunopathol. 2013;156(1–2):99–106.

    Article  CAS  PubMed  Google Scholar 

  41. Eliopoulos N, Stagg J, Lejeune L, Pommey S, Galipeau J. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood. 2005;106(13):4057–65.

    Article  CAS  PubMed  Google Scholar 

  42. Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE. Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood. 2006;108(6):2114–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zangi L, Margalit R, Reich-Zeliger S, et al. Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells. Stem Cells. 2009;27(11):2865–74.

    Article  CAS  PubMed  Google Scholar 

  44. Marks PW, Witten CM, Califf RM. Clarifying stem-cell therapy’s benefits and risks. N Engl J Med. 2016;376(11):1007–9.

    Article  PubMed  Google Scholar 

  45. Kuriyan AE, Albini TA, Townsend JH, et al. Vision loss after intravitreal injection of autologous "stem cells" for AMD. N Engl J Med. 2017;376(11):1047–53.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Berkowitz AL, Miller MB, Mir SA, et al. Glioproliferative lesion of the spinal cord as a complication of "stem-cell tourism". N Engl J Med. 2016;375(2):196–8.

    Article  PubMed  Google Scholar 

  47. Bauer G, Elsallab M, Abou-El-Enein M. Concise review: a comprehensive analysis of reported adverse events in patients receiving unproven stem cell-based interventions. Stem Cells Transl Med. 2018;7(9):676–85.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Murray IR, Chahla J, Safran MR, et al. International expert consensus on a cell therapy communication tool: DOSES. J Bone Joint Surg Am. 2019;101(10):904–11.

    Article  PubMed  Google Scholar 

  49. de Windt TS, Vonk LA, Slaper-Cortenbach ICM, Nizak R, van Rijen MHP, Saris DBF. Allogeneic MSCs and recycled autologous chondrons mixed in a one-stage cartilage cell transplantation: a first-in-man trial in 35 patients. Stem Cells. 2017;35(8):1984–93.

    Article  PubMed  CAS  Google Scholar 

  50. https://www.clinicaltrials.gov/. Published 2020. Accessed 2/21/2020, 2020.

  51. Marks P, Gottlieb S. Balancing safety and innovation for cell-based regenerative medicine. N Engl J Med. 2018;378(10):954–9.

    Article  PubMed  Google Scholar 

  52. Murray IR, Murray AD, Geeslin AG, et al. Infographic: we need minimum reporting standards for biologics. Br J Sports Med. 2019;53(15):974–5.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, Division of Sports Medicine, Mayo Clinic, Rochester, MN, USA

    Lucas K. Keyt, Matthew D. LaPrade, Aaron J. Krych & Daniel B. F. Saris

  2. Department of Orthopedics, University Medical Center, Utrecht, The Netherlands

    Daniel B. F. Saris

Authors
  1. Lucas K. Keyt
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  2. Matthew D. LaPrade
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  3. Aaron J. Krych
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  4. Daniel B. F. Saris
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Corresponding author

Correspondence to Daniel B. F. Saris .

Editor information

Editors and Affiliations

  1. Rizzoli Orthopaedic Institute, Bologna, Italy

    Giuseppe Filardo

  2. Orthopaedic & Sports Medicine Group, Santa Monica Orthopaedic & Sports Medicine, Santa Monica, CA, USA

    Bert R. Mandelbaum

  3. Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA

    George F. Muschler

  4. Hospital for Special Surgery, New York, NY, USA

    Scott A. Rodeo

  5. Institute for Medical Science in Sports, Osaka Health Science University, Osaka, Japan

    Norimasa Nakamura

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Keyt, L.K., LaPrade, M.D., Krych, A.J., Saris, D.B.F. (2022). Injectable Allogenic Mesenchymal Stromal Cells: Advantages, Disadvantages, and Challenges. In: Filardo, G., Mandelbaum, B.R., Muschler, G.F., Rodeo, S.A., Nakamura, N. (eds) Orthobiologics. Springer, Cham. https://doi.org/10.1007/978-3-030-84744-9_6

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  • DOI: https://doi.org/10.1007/978-3-030-84744-9_6

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