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Identification of the Human Skeletal Stem Cell
Charles K F Chan1, Gunsagar S Gulati1, Rahul Sinha2
1Department of Surgery, Stanford Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medicine, Stanford, CA 94305, USA.
Cell
|September 23, 2018
Summary
Researchers isolated self-renewing, multipotent human skeletal stem cells (hSSCs) from bone, iPSCs, and adipose tissue. These hSSCs generate bone, cartilage, and stroma, aiding skeletal repair and supporting hematopoietic stem cells.
Area of Science:
- Regenerative Medicine
- Developmental Biology
- Stem Cell Biology
Background:
- The hierarchical organization and regulation of human skeletal stem cells (hSSCs) are not well understood.
- Identifying and characterizing hSSCs is crucial for understanding skeletal development and repair.
Purpose of the Study:
- To isolate and characterize self-renewing, multipotent human skeletal stem cells (hSSCs).
- To investigate the potential of hSSCs in generating various skeletal lineages and their role in skeletal injury.
- To compare gene expression and epigenetic data between human and mouse skeletal stem cells.
Main Methods:
- Isolation of hSSCs from fetal and adult human bones, BMP2-treated adipose stroma (B-HAS), and induced pluripotent stem cells (iPSCs).
- Single-cell gene expression analysis of isolated hSSCs.
- Assessment of hSSC differentiation potential towards bone, cartilage, and stroma.
- In vivo studies on hSSC response to skeletal injury.
- Analysis of hSSC-derived stroma for hematopoietic stem cell maintenance.
- Comparative analysis of gene expression and epigenetic data between human and mouse skeletal stem cells (mSSCs).
Main Results:
- Isolation of self-renewing and multipotent hSSCs capable of generating bone, cartilage, and stroma, but not fat.
- hSSCs were found in fetal and adult bones, and could be derived from B-HAS and iPSCs.
- Gene expression analysis revealed similarities among hSSCs from different sources, with some skewing towards cartilage differentiation in fetal and iPSC-derived cells.
- hSSCs demonstrated local expansion in response to acute skeletal injury.
- hSSC-derived stroma supported human hematopoietic stem cell (hHSC) maintenance in serum-free conditions.
- Identification of conserved and divergent pathways in skeletogenesis between human and mouse SSCs.
Conclusions:
- A distinct population of self-renewing, multipotent human skeletal stem cells (hSSCs) has been identified and characterized.
- hSSCs play a role in skeletal repair and can support hematopoietic stem cells, highlighting their therapeutic potential.
- Comparative analysis provides insights into conserved and divergent mechanisms of skeletal stem cell function across species.
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