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Home / Equine Research Bank / Stem Cell Res Ther / Multi-differentiation potential is necessary for optimal ten...
Stem cell research & therapy2020; 11(1); 152; doi: 10.1186/s13287-020-01640-8

Multi-differentiation potential is necessary for optimal tenogenesis of tendon stem cells.

Abstract: Tendon injury is a significant clinical problem due to poor healing and a high reinjury rate; successful treatment is limited by our poor understanding of endogenous tendon stem cells. Recent evidence suggests that adult stem cells are phenotypically diverse, even when comparing stem cells isolated from the same tissue from the same individual, and may in fact exist on a spectrum of proliferation and differentiation capacities. Additionally, the relationships between and clinical relevance of this phenotypic variation are poorly understood. In particular, tenogenic capacity has not been studied in comparison to tenogenic differentiation and cell proliferation. Toward this end, we performed a comprehensive assessment of cell proliferation and differentiation capacity toward four connective tissue lineages (tendon, cartilage, bone, and adipose) using tendon stem cell lines derived from single cells released directly from tendon tissue to (1) evaluate the differences, if any, in tenogenic potential, and (2) identify the relationships between differentiation phenotypes and proliferation capacity. Tendon stem cells were derived from the endotenon of superficial digital flexor tendon from 3 horses. The cell suspension from each horse was separately plated simultaneously (1) at moderate density to generate a heterogenous population of cells-parent tendon cell line-and (2) at low density to separate single cells from each other to allow isolation of colonies that derive from single mother cells-clonal tendon stem cell lines. Thirty clonal tendon stem cell lines-10 from each horse-and each parent tendon cell line were assessed for tenogenesis, tri-lineage differentiation, and cell proliferation. Differentiation was confirmed by lineage-specific cell staining and quantified by the relative gene expression of lineage-specific markers. Statistical significance was determined using analysis of variance and post hoc Tukey's tests. Three distinct differentiation phenotypes-differentiation potency toward all 4 tissue lineages and two tri-lineage differentiation potencies-were identified in tendon clonal stem cell lines. These phenotypes were differentiation toward (1) tendon, cartilage, bone, and adipose (TCOA); (2) tendon, cartilage, and bone (TCO); and (3) tendon, cartilage, and adipose (TCA). Further, clonal cell lines that differentiated toward all four lineages had the highest expression of scleraxis and mohawk upon tenogenesis. Moreover, cell proliferation was significantly different between phenotypic groups, as evidenced by increased numbers of cumulative cell population doublings in clonal cell lines that did not differentiate toward adipose. Our study provides evidence of the heterogenous character of adult stem cells and identifies key differences in tendon stem cell differentiation and proliferative potentials from the same individual and from the same tendon. Isolation of tendon stem cell lines with the capacity to differentiate into all four connective tissue lineages may yield improved therapeutic benefits in clinical models of repair and promote a native, regenerative phenotype in engineered tendons. Future studies may be targeted to understanding the functional contributions of each tendon stem cell phenotype in vivo and identifying additional cell phenotypes.
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Publication Date: 2020-04-09 PubMed ID: 32272975PubMed Central: PMC7146987DOI: 10.1186/s13287-020-01640-8Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the diverse abilities of tendon stem cells to differentiate into the four main connective tissue types – tendon, cartilage, bone, and adipose tissue – and how this potential can be harnessed to better treat tendon injuries, which are currently difficult to manage due to poor healing and high reinjury rates.

Study Design and Methodology

  • Tendon stem cells were harvested from the superficial digital flexor tendon of three horses. Each sample was plated at both moderate and low densities to generate a mixed community of cells and single-cell colonies respectively.
  • These cellular lines, a total of thirty distinct stem cell lines from each horse plus the parent cells, were then tested for their potential to differentiate into the four main connective tissue lineages.
  • Lineage-specific staining and gene expression analysis were used to confirm differentiation into each type of tissue.

Findings

  • The results demonstrated three distinct phenotypes signifying the different differentiation potentials. The first group could differentiate into all four tissue types (tendon, cartilage, bone, and adipose). The second group exhibited tri-lineage differentiation towards tendon, cartilage, and bone. The third group showed a tendency to differentiate into tendon, cartilage, and adipose.
  • Cells which could differentiate into all four tissue types showed the highest expression of certain genes (scleraxis and mohawk) related to tendon creation.
  • Interestingly, the study found correlation between a cell’s differentiation potential and its proliferation capacity. Cell lines that did not differentiate into adipose tissue had significantly greater proliferation, indicating a link between differentiation ability and growth capacity.

Implication and Future Research

  • This study expanded the understanding of tendon stem cells’ differentiation ability and their variability. These findings could be critical to improving therapies for tendon injuries, potentially leading to better healing and decreased reinjury rates.
  • Isolating and utilizing tendon stem cells with multi-differentiation potentials may lead to improved tissue repair and promote a more natural healing response in tendon injuries.
  • Further research needs to investigate the role of each phenotype during tendon healing in vivo, possibly identifying additional phenotypes which could be used for specific therapeutic strategies.

Cite This Article

APA
Rajpar I, Barrett JG. (2020). Multi-differentiation potential is necessary for optimal tenogenesis of tendon stem cells. Stem Cell Res Ther, 11(1), 152. https://doi.org/10.1186/s13287-020-01640-8

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 152
PII: 152

Researcher Affiliations

Rajpar, Ibtesam
  • Department of Large Animal Clinical Sciences, Marion duPont Scott Equine Medical Center, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Leesburg, 17690 Old Waterford Road, Leesburg, VA, 20176, USA.
Barrett, Jennifer G
  • Department of Large Animal Clinical Sciences, Marion duPont Scott Equine Medical Center, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Leesburg, 17690 Old Waterford Road, Leesburg, VA, 20176, USA. jgbarrett@vt.edu.

MeSH Terms

  • Adipose Tissue
  • Animals
  • Cell Differentiation
  • Horses
  • Mesenchymal Stem Cells
  • Stem Cells
  • Tendons
  • Tissue Engineering

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 12 times.
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