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Clinical Variables that Influence Properties of Human Mesenchymal Stromal Cells

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Abstract

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.

Lay Summary

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.

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Funding

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.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA

    Julie Glowacki, Jessica J. Alm & Shuanhu Zhou

  2. Department of Oral & Maxillofacial Surgery, Harvard School of Dental Medicine, Boston, MA, USA

    Julie Glowacki

  3. Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

    Jessica J. Alm

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  1. Julie Glowacki
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Glowacki, J., Alm, J.J. & Zhou, S. Clinical Variables that Influence Properties of Human Mesenchymal Stromal Cells. Regen. Eng. Transl. Med. 6, 310–321 (2020). https://doi.org/10.1007/s40883-019-00123-4

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