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Related Concept Videos

Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their access...
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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...

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Paracrine interactions between mesenchymal stem cells affect substrate driven differentiation toward tendon and bone

Ram I Sharma1, Jess G Snedeker

  • 1Department of Orthopedics, University of Zurich-Balgrist, Zurich, Switzerland.

Plos One
|February 23, 2012
PubMed
Summary

Biomaterials guide bone marrow stromal cell (BMSC) differentiation for tendon-to-bone healing. Paracrine signals from tenogenic cells, potentially via bone morphogenetic protein-2 (BMP-2), can inhibit osteogenesis.

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Comparison of Two Representative Methods for Differentiation of Human Induced Pluripotent Stem Cells into Mesenchymal Stromal Cells

Published on: October 20, 2023

Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Cell Biology

Background:

  • The tendon to bone enthesis is a critical interface for musculoskeletal function.
  • Understanding cell signaling during enthesis regeneration is crucial for developing effective therapies.
  • Bone marrow stromal cells (BMSCs) play a key role in this regenerative process.

Purpose of the Study:

  • To investigate substrate-dependent paracrine signaling between BMSC subpopulations.
  • To explore how substrate mechanics and biochemistry influence BMSC differentiation towards osteogenic and tenogenic lineages.
  • To identify signaling pathways, such as bone morphogenetic protein-2 (BMP-2), involved in regulating BMSC fate at the enthesis.

Main Methods:

  • Culture of BMSCs on polyacrylamide substrates with varying elastic moduli (10-90 kPa) and mechanical gradients.
  • Substrate functionalization with fibronectin (Fn), type-I collagen (Col), or a combination (Fn/Col).
  • Supplementation of culture media with soluble Col or Fn, and assessment of BMP-2 effects.

Main Results:

  • Rigid substrates (70-90 kPa) with narrow gradients induced osteogenic differentiation on both Col and Fn.
  • Broader gradient substrates (10-90 kPa) showed osteogenic differentiation on Fn above 20 kPa, but this was inhibited by Col.
  • Tenogenic differentiation occurred on moderately rigid Col substrates (30-50 kPa), and co-culture studies revealed paracrine inhibition of osteogenesis by tenogenic cells, mediated by BMP-2.

Conclusions:

  • Engineered biomaterials can direct BMSC differentiation for tendon-to-bone healing.
  • Substrate mechanics and ligand presentation critically influence cell fate decisions.
  • Paracrine signaling from tenogenic cells, particularly BMP-2, can impede osteogenic differentiation at the healing enthesis.