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Intramyocardial Transplantation of MSC-Loading Injectable Hydrogels after Myocardial Infarction in a Murine Model
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In vitro MSC function is related to clinical reaction in vivo

Aileen L Rowland1, Jiajie Jessica Xu1, Amanda Jo Joswig1

  • 1Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.

Stem Cell Research & Therapy
|November 10, 2018
PubMed
Abstract

Insights

Mesenchymal stem cells (MSCs) with higher stemness showed reduced immunogenicity in horses, unlike xenogen-contaminated cells. This suggests improved stemness may correlate with a better clinical response after intra-articular injection.

Area of Science:

  • Veterinary Medicine
  • Regenerative Medicine
  • Immunology

Background:

  • Previous studies showed xenogen-contaminated autologous MSCs (FBS) and allogeneic MSCs (ALLO) caused adverse responses in horses after intra-articular injection.
  • Autologous (AUTO) MSCs, free from xenogen contamination, did not elicit adverse reactions.
  • This study aimed to correlate MSC stemness with adverse clinical responses, using synovial total nucleated cell count (TNCC) as an indicator.

Purpose of the Study:

  • To compare mesenchymal stem cell (MSC) stemness against adverse clinical responses in horses post-injection.
  • To evaluate the relationship between MSC stemness, immunomodulation, MHCI expression, and synovial total nucleated cell count (TNCC).

Main Methods:

  • Stemness was quantified using a trilineage differentiation (TLD) score.
  • Immunomodulation was assessed via mixed lymphocyte reactions (MLRs).
  • MHCI expression was measured by mean fluorescent intensity (MFI) and correlated with TNCC post-injection.

Main Results:

  • A trend of negative correlation between TLD score and TNCC was observed in the allogeneic (ALLO) group after primed injection.
  • A significant positive correlation between MHCI MFI and TNCC was found in the ALLO group after naïve injection.
  • Lymphocyte proliferation positively correlated with TNCC in the xenogen-contaminated autologous MSCs (FBS) group.

Conclusions:

  • Improved MSC stemness appears associated with reduced immunogenicity, as indicated by a trend of negative correlation with TNCC in the ALLO group.
  • In vitro immunomodulatory activity (MLRs) correlated with in vivo adverse responses, especially when xenogen contamination was present.
  • Further investigation is warranted to elucidate the relationship between in vitro stemness, immunomodulation, MHCI expression, and in vivo clinical outcomes.
Keywords:
AllogeneicBone marrowHorseImmunogenicityIntra-articularJointMSCStemnessTrilineage differentiation

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