# Identifying the human skeletal stem cell.

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $381,614

## Abstract

Project Summary
The primary goal of this proposed project is to identify and characterize the human skeletal stem cell (hSSC)
and the lineage restricted progenitors of bone, cartilage, and bone marrow stromal tissues that it generates.
Building on our recent publication in Cell detailing the mouse SSC, our ultimate objective is to create a detailed
lineage map of human skeletogenesis, as seen in hematopoiesis, with a mulitpotent stem cell generating various
lineages in a niche that regulates differentiation. As demonstrated in our mouse study, we will achieve this by
first purifying human skeletal stem and progenitor cells to a very high level of homogeneity (Aim 1) and then
secondly by examining the transcriptional and translational expression of the cellular subsets, before finally
defining and probing the inter-relationship between the stem and progenitor cells. These steps will, thus, enable
us to strategize how to manipulate the SSC niche to drive fate determination of bone, cartilage or bone marrow
stroma to affect clinical need (Aim 2). Our investigation of the mSSC niche regulation also led us to discover
specific combinations of bone morphogenetic protein-2, Wnt and VEGF that could induce de novo formation of
SSC even in non-skeletal (adipose) tissue. We will explore if similar morphogen combinations could also induce
hSSC formation and de novo generation of bone, cartilage, or stroma from plentiful human adipose stromal
populations (Aim 3).
Despite the utility of mouse models, recent reports describe dramatic differences between mouse and human
immunology, which has a direct impact on the development of novel therapeutics. Therefore, in order to truly
affect clinical translation, it is prudent to first identify the hSSC to identify key genetic pathways that are conserved
in mouse and human skeletogenesis and to reveal the genetic mechanisms underlying differences between
mouse and humans. We are confident that the expertise we acquired upon implementation of our mSSC strategy
puts us in a unique position to characterize human counterparts of the mouse skeletal stem and progenitor cell.
Our new substantial preliminary human skeletal stem/progenitor data from both fetal and adult tissue strongly
affirm the technical feasibility of our approach and the existence of the hSSC. The proposed experiments in this
application, if supported, would clear the path to practical translation of stem cell regenerative medicine for
skeletal diseases.

## Key facts

- **NIH application ID:** 9975006
- **Project number:** 5R01DE027323-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** MICHAEL T LONGAKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,614
- **Award type:** 5
- **Project period:** 2018-08-06 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975006

## Citation

> US National Institutes of Health, RePORTER application 9975006, Identifying the human skeletal stem cell. (5R01DE027323-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9975006. Licensed CC0.

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