Clinical Variables that Influence Properties of Human Mesenchymal Stromal Cells
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Many bone tissue engineering studies use animal or immortalized human mesenchymal stromal cells (hMSCs), which include osteoblast progenitors, because of the abundance of those cells. It is advantageous to study the less plentiful human MSCs in research on bone tissue engineering because of the clinical relevance and because of the importance of discovering how to optimize hMSCs for autogenous use. There is growing evidence that some of the irreproducibility in biological experiments with hMSCs can be attributed to variable clinical characteristics of the subjects from whom they were obtained. Patients who could benefit from bone tissue engineering are likely to have cellular deficits and compromised biochemical milieu, some of which can be managed by customized in vitro treatments. Many donor characteristics are associated with their hMSC in vitro properties. Studies with cohorts with similar characteristics show that some deficits are modifiable in vitro and can be managed with greater understanding of their pathophysiological mechanisms. Even hMSCs from elders can be rejuvenated in vitro with safe agents. Additional value in studying physiology of hMSCs from characterized subjects is to develop rationales for new in vivo therapies to ensure skeletal health throughout the lifespan.
During this era of intensive tissue engineering research, it is appealing to use human mesenchymal stromal cells (hMSCs) for bone tissue engineering research because of their clinical relevance. Use of the patient’s own cells for therapeutic applications is called autogenous cell-based therapy. Research shows that properties of hMSCs isolated from a subject’s marrow depend on many clinical characteristics and that, in some cases, their osteoblast differentiation potential in cell culture can be optimized safely. These observations also suggest ways to optimize the functions of the skeleton throughout the lifespan.
KeywordsMesenchymal stem cells MSCs Human In vitro Osteoblast differentiation Aging Co-morbidities
This work was supported by grants from the Department of Orthopedic Surgery, Brigham and Women‘s Hospital, and The Gillian Reny Stepping Strong Center for Trauma Innovation. JJA is supported by grants from The Finnish Cultural Foundation, The M. Borgstrom Foundation, Erik & Edith Fernstrom Foundation, the Maud Kuistila Memorial Foundation, and by an award from the ASBMR Fund for Research and Education.
- 3.Owen M, Friedenstein AJ. Stromal stem cells: marrow-derived osteogenic precursors. CIBA Found Symp. 1988;136:42–60.Google Scholar
- 4.Friedenstein AJ. Stromal mechanisms of bone marrow: cloning in vitro and retransplantation in vivo. In: Theinfelder S, editor. Immunobiology of bone marrow transplantation. Berlin: Springer-Verlag. p. 19–29.Google Scholar
- 7.Falster C, Poulsen SS, Storaas AM, Schroeder HM, Vinther JH, Kassem M, Joergensen U. Mesenchymal stem cells isolated from both distal femurs of patients with unilateral trauma or osteoarthritis of the knee exhibit similar in-vitro ability of bone formation. J Orthop Sci. 2019.Google Scholar
- 12.Alm JJ, Qian H, Le Blanc K. Clinical grade production of mesenchymal stromal cells. In: Blitterswijk C, DeBoer J, editors. Tissue engineering. 2nd ed: Academic Press; 2014. p. 427–70.Google Scholar
- 31.Aizawa S, Yaguchi M, Nakano M, Toyama K, Inokuchi S, Imai T, et al. Hematopoietic supportive function of human bone marrow stromal cell lines established by a recombinant SV40-adenovirus vector. Exp Hematol. 1994;22:482–7.Google Scholar
- 44.Zhou S, Glowacki J, Kim SW, Hahne J, Geng S, Mueller SM, et al. Clinical characteristics influence in vitro action of 1,25-dihydroxyvitamin D(3) in human marrow stromal cells. J Bone Miner Res. 2012:271992–2000.Google Scholar
- 57.Gonnelli S, Caffarelli C, Nuti R. Obesity and fracture risk. Clin Cases Miner Bone Metab. 2014;11:9–14.Google Scholar
- 63.Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, et al. Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab. 2001;86:1884–7.Google Scholar
- 64.Reid IR, Baldock PA, Cornish J. Effects of leptin on the skeleton. Endocr Rev. 2018;39:938–59.Google Scholar
- 67.Li J, Glowacki J, LeBoff M, Zhou S. Vitamin D metabolism in human mesenchymal stem cells: Effects of body composition and leptin. Am Soc Bone Mineral Res, 2016, Atlanta GA. http://www.asbmr.org/education/AbstractDetail?aid=d7ceb348-a153-4dc8-b0fc-8b8ff72db5e8.
- 70.Krampera M, Galipeau J, Shi Y, Tarte K, Sensebe L, MSC Committee of the International Society for Cellular Therapy (ISCT). Immunological characterization of multipotent mesenchymal stromal cells--The International Society for Cellular Therapy (ISCT) working proposal. Cytotherapy. 2013;15:1054–61.CrossRefGoogle Scholar
- 74.Cheleuitte D, Mizuno S, Glowacki J. In vitro secretion of cytokines of human bone marrow: effects of age and estrogen status. J Clin Endocrinol Metab. 1998;83:2043–51.Google Scholar
- 78.Alm JJ. Bone quality and mesenchymal stromal cell capacity in total hip replacement: significance for stem osseointegration measured by radiostereometric analysis. Annales Universitatis Turkuensis D 2016;1244. http://urn.fi/URN:ISBN:978-951-29-6580-9.