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REVIEW
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Recent updates on the biological basis of  heterogeneity in bone marrow stromal cells/ skeletal stem cells

Deepika Arora1,2,3 ,  Pamela Gehron Robey1*
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1 National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
2 Biosystems and Biomaterials Division, National Institute of Standards and Technology, Department of Commerce, Gaithersburg, MD, USA
3 Department of Biotechnology, School of Biological Engineering & Life Sciences, Shobhit Institute of Engineering & Technology (Deemed-to-be-University), Meerut, India
BMT 2022 , 3(1), 3–16; https://doi.org/10.12336/biomatertransl.2022.01.002
Submitted: 20 January 2022 | Revised: 17 March 2022 | Accepted: 20 March 2022 | Published: 28 March 2022
Copyright © 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Based on studies over the last several decades, the self-renewing skeletal lineages derived from bone marrow stroma could be an ideal source for skeletal tissue engineering. However, the markers for osteogenic precursors; i.e., bone marrow-derived skeletal stem cells (SSCs), in association with other cells of the marrow stroma (bone marrow stromal cells, BMSCs) and their heterogeneous nature both in vivo and in vitro remain to be clarified. This review aims to highlight: i) the importance of distinguishing BMSCs/SSCs from other “mesenchymal stem/stromal cells”, and ii) factors that are responsible for their heterogeneity, and how these factors impact on the differentiation potential of SSCs towards bone. The prospective role of SSC enrichment, their expansion and its impact on SSC phenotype is explored. Emphasis has also been given to emerging single cell RNA sequencing approaches in scrutinizing the unique population of SSCs within the BMSC population, along with their committed progeny. Understanding the factors involved in heterogeneity may help researchers to improvise their strategies to isolate, characterize and adopt best culture practices and source identification to develop standard operating protocols for developing reproducible stem cells grafts. However, more scientific understanding of the molecular basis of heterogeneity is warranted that may be obtained from the robust high-throughput functional transcriptomics of single cells or clonal populations.

Keywords
bone marrow stromal cells; clonal analysis; heterogeneity; single cell analysis; skeletal stem cells
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Conflict of interest
The authors declare they have no competing interests.
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