Evidence map›Paper›PMID 37316563›Full record

ReviewNature protocols2023

Purification and functional characterization of novel human skeletal stem cell lineages.

Malachia Y Hoover, Thomas H Ambrosi, Holly M Steininger, Lauren S Koepke, Yuting Wang, Liming Zhao, Matthew P Murphy, Alina A Alam, Elizabeth J Arouge, M Gohazrua K Butler and 12 more

Open access · greenAbstract readReview
In one paragraph

Review in Nature protocols, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
8.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Bioprinted Organoids: An Innovative Engine in Biomedicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Nanodrug-Engineered Exosomes Achieve a Jointly Dual-Pathway Inhibition on Cuproptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Exosomes derived from CD271Theranostics · 2024
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 8 institutions in 4 countries.

Malachia Y Hoover *Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Thomas H Ambrosi *Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Holly M Steininger *Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-8098-3753
Lauren S Koepke *Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Yuting Wang *Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Liming ZhaoInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Matthew P MurphyInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-0885-4089
Alina A AlamInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Elizabeth J ArougeInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
M Gohazrua K ButlerInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Eri TakematsuInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Suzan P StavitskyInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Serena HuDepartment of Orthopaedic Surgery, Stanford Hospitals and Clinics, Stanford, CA, USA.
Debashis SahooDepartment of Pathology, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0003-2329-8228
Rahul SinhaInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Maurizio MorriChan Zuckerberg BioHub, San Francisco, CA, USA.
Norma NeffChan Zuckerberg BioHub, San Francisco, CA, USA.
Julius BishopDepartment of Orthopaedic Surgery, Stanford Hospitals and Clinics, Stanford, CA, USA.
Michael GardnerDepartment of Orthopaedic Surgery, Stanford Hospitals and Clinics, Stanford, CA, USA.
Stuart GoodmanDepartment of Orthopaedic Surgery, Stanford Hospitals and Clinics, Stanford, CA, USA.
Michael LongakerInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-1430-8914
Charles K F ChanInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA. chazchan@stanford.edu.ORCID 0000-0001-6570-7574
Stanford University · USStanford Health Care · USChan Zuckerberg Biohub San Francisco · USTongji Hospital · CNCalifornia Institute for Regenerative Medicine · USManchester Academic Health Science Centre · GBUC Davis Health · USUniversity of California San Diego · US

Funding

Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2M
Center for Dental, Oral, and Craniofacial Tissue and Organ Regeneration (C-DOCTOR)U24DE026914 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAI, YANG, CHEN, YONG · 2017 to 2019
$12.0M
Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
Interrogation of individual cells to identify progenitors and their nichesU01HL099999 · NHLBI · STANFORD UNIVERSITY · PI WEISSMAN, IRVING L. · 2009 to 2015
$7.8M
HSC Diversity: Regulation by Clonal Selection vs Epigenetic InductionR01CA086065 · NCI · STANFORD UNIVERSITY · PI WEISSMAN, IRVING L. · 2000 to 2017
$6.9M
HOMING RECEPTOR DETERMINANTS ON HSCR01HL058770 · NHLBI · STANFORD UNIVERSITY · PI WEISSMAN, IRVING L. · 1998 to 2013
$3.9M
Wear Particle Disease and NF-kappa B SignalingR01AR063717 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2012 to 2021
$3.5M
Chemokine Directed Cell Trafficking during Continuous Infusion of Wear ParticlesR01AR055650 · NIAMS · STANFORD UNIVERSITY · PI GOODMAN, STUART B · 2007 to 2016
$3.3M
Osteogenic Enrichment of Adipose Derived Stromal CellsR01DE021683 · NIDCR · STANFORD UNIVERSITY · PI GURTNER, GEOFFREY C, LONGAKER, MICHAEL T · 2012 to 2016
$2.0M
Identifying the human skeletal stem cell.R01DE027323 · NIDCR · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T · 2018 to 2022
$1.9M
Cellular and Mechanical Mechanisms Regulating Mandibular Distraction OsteogenesisR01DE026730 · NIDCR · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T · 2017 to 2021
$1.9M
Cellular and molecular analyses of hematopoietic stem cell [HSC] interactions with bone marrow niches to improve HSC engraftment for transplantation and tolerance inductionR01DK115600 · NIDDK · STANFORD UNIVERSITY · PI WEISSMAN, IRVING L. · 2018 to 2021
$1.5M
BLRD VA I01 BX003754NCI NIH HHS R01 CA086065NHGRI NIH HHS P50 HG007735NHLBI NIH HHS R01 HL058770NHLBI NIH HHS U01 HL099776NHLBI NIH HHS U01 HL099999NIAMS NIH HHS R01 AR055650NIAMS NIH HHS R01 AR063717NIA NIH HHS K99 AG049958NIA NIH HHS K99 AG066963NIA NIH HHS R00 AG049958NIA NIH HHS R00 AG066963NIDCR NIH HHS R01 DE021683NIDCR NIH HHS R01 DE026730NIDCR NIH HHS R01 DE027323NIDCR NIH HHS R21 DE019274NIDCR NIH HHS R21 DE024230NIDCR NIH HHS R56 DE025597NIDCR NIH HHS U24 DE026914NIDDK NIH HHS R01 DK115600NIGMS NIH HHS K08 GM069677NIH HHS S10 OD028493
6 · The paper itself

Abstract

Human skeletal stem cells (hSSCs) hold tremendous therapeutic potential for developing new clinical strategies to effectively combat congenital and age-related musculoskeletal disorders. Unfortunately, refined methodologies for the proper isolation of bona fide hSSCs and the development of functional assays that accurately recapitulate their physiology within the skeleton have been lacking. Bone marrow-derived mesenchymal stromal cells (BMSCs), commonly used to describe the source of precursors for osteoblasts, chondrocytes, adipocytes and stroma, have held great promise as the basis of various approaches for cell therapy. However, the reproducibility and clinical efficacy of these attempts have been obscured by the heterogeneous nature of BMSCs due to their isolation by plastic adherence techniques. To address these limitations, our group has refined the purity of individual progenitor populations that are encompassed by BMSCs by identifying defined populations of bona fide hSSCs and their downstream progenitors that strictly give rise to skeletally restricted cell lineages. Here, we describe an advanced flow cytometric approach that utilizes an extensive panel of eight cell surface markers to define hSSCs; bone, cartilage and stromal progenitors; and more differentiated unipotent subtypes, including an osteogenic subset and three chondroprogenitors. We provide detailed instructions for the FACS-based isolation of hSSCs from various tissue sources, in vitro and in vivo skeletogenic functional assays, human xenograft mouse models and single-cell RNA sequencing analysis. This application of hSSC isolation can be performed by any researcher with basic skills in biology and flow cytometry within 1-2 days. The downstream functional assays can be performed within a range of 1-2 months.

Indexed as

Mesenchymal Stem CellsAnimalsBone and BonesBone Marrow CellsCell DifferentiationCell LineageCells, CulturedHumansMiceReproducibility of Results

Identifiers

PMID37316563
PMCPMC10495180
OpenAlexW4380550630

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.