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Stem cell research & therapy2018; 9(1); 295; doi: 10.1186/s13287-018-1037-4

In vitro MSC function is related to clinical reaction in vivo.

Abstract: We recently demonstrated that intracellular xenogen-contaminated autologous MSCs (FBS) and non-xenogen-contaminated allogeneic (ALLO) MSCs caused an adverse clinical response after repeated intra-articular injection in horses, whereas autologous (AUTO) MSCs did not. Our current objective was to use clinical data from the previous study to compare MSC stemness against adverse response indicated by synovial total nucleated cell count (TNCC) following intra-articular MSC injection. Stemness, quantified by a trilineage differentiation (TLD) score; immunomodulation, quantified by mixed lymphocyte reactions (MLRs); and degree of MHCI expression, quantified by mean fluorescent intensity (MFI); were correlated to the synovial TNCC 24 h after naïve and primed injection. There was a trend of a negative correlation (p = 0.21, r = - 0.44) between TLD score and TNCC after primed injection in the ALLO group. Within the ALLO group only, there was a significant positive correlation (p = 0.05, r = 0.77) between MHCI MFI and TNCC after naïve injection and a trend (p = 0.16, r = 0.49) of a positive association of MHCI MFI to TNCC after primed injection. Within the FBS group only, there was a positive correlation (p = 0.04, r = 1) between TNCC and lymphocyte proliferation after both injections. The trend of a negative correlation of TLD score and TNCC in the ALLO, but not the FBS group, together with the association of MHCI expression and TNCC in the ALLO group, indicates that improved stemness is associated with reduced MSC immunogenicity. When inflammation was incited by xenogen, there was a strong correlation of lymphocyte activation in vitro to adverse response in vivo, confirming that MLRs in vitro reflect MSC immunomodulatory activity in vivo. The relationship of stemness in vitro, suppression of lymphocyte activation in vitro, MHCI expression in vitro, and clinical response in vivo should be further investigated.
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Publication Date: 2018-11-08 PubMed ID: 30409211PubMed Central: PMC6225557DOI: 10.1186/s13287-018-1037-4Google 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 looks into the correlation between the functions of Mesenchymal Stem Cells (MSCs) in vitro (in a controlled environment) and their reactions in vivo (inside the body). The study specifically examines the clinical responses seen in horses after repeated intra-articular injections of different types of MSCs and how these reactions relate to measures of MSC ‘stemness’, immunomodulation and MHCI expression in vitro.

Research Objectives and Methodology

  • The main purpose of this study was to understand how the ‘stemness’ (ability to reproduce into various types of cells) of MSCs relates to adverse reactions in horses, measured by the synovial total nucleated cell count (TNCC), after intra-articular injections.
  • The study looked at laboratory (in vitro) measurements of stemness using a Trilineage Differentiation (TLD) score, immunomodulation using the results of Mixed Lineage Reactions (MLRs), and MHCI expression using the mean fluorescent intensity (MFI).
  • The researchers compared these laboratory measurements to clinical outcomes in horses after injecting autologous MSCs (from the same individual), xenogen-contaminated autologous MSCs (MSCs from the same individual but contaminated with materials from a different species), and non-xenogen-contaminated allogeneic MSCs (MSCs from a different individual of the same species).

Research Findings

  • A trend of negative correlation was observed in the ALLO group between the TLD score (stemness) and the TNCC after the primed injection, which suggests that a higher level of stemness could lead to a reduced adverse response.
  • In the ALLO group, there was a significant positive correlation between the MHCI MFI (a measure of an immune response) and the TNCC after the naïve injection. There was also a trend of the same positive correlation after the primed injection.
  • In the FBS group, a positive correlation was observed between TNCC and lymphocyte proliferation after both injections.

Conclusions

  • The results suggest that an improved level of stemness in MSCs could be associated with their lower immunogenicity.
  • Also, when inflammation was caused by xenogen, there was a strong relationship between lymphocyte activation in the lab and the adverse response inside the body. This reaffirms the notion that the in-vitro MLRs mirror the in-vivo immunomodulatory activity of the MSCs.
  • Further research should be carried out to understand the connection between in-vitro stemness, suppression of lymphocyte activation, MHCI expression, and the in-vivo clinical response of the MSCs.

Cite This Article

APA
Rowland AL, Xu JJ, Joswig AJ, Gregory CA, Antczak DF, Cummings KJ, Watts AE. (2018). In vitro MSC function is related to clinical reaction in vivo. Stem Cell Res Ther, 9(1), 295. https://doi.org/10.1186/s13287-018-1037-4

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 9
Issue: 1
Pages: 295
PII: 295

Researcher Affiliations

Rowland, Aileen L
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.
Xu, Jiajie Jessica
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.
Joswig, Amanda Jo
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.
Gregory, Carl A
  • Department of Molecular and Cellular Medicine, Institute for Regenerative Medicine, Texas A&M Health Science Center, College Station, TX, USA.
Antczak, Douglas F
  • Department of Microbiology and Immunology, Cornell University, Ithaca, NY, USA.
Cummings, Kevin J
  • Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY, USA.
Watts, Ashlee E
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA. awatts@cvm.tamu.edu.

MeSH Terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Fluorescence
  • Haplotypes
  • Histocompatibility Antigens Class I / metabolism
  • Horses
  • Lymphocyte Culture Test, Mixed
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Time Factors

Conflict of Interest Statement

ETHICS APPROVAL: This study was approved by the university’s Institutional Animal Care and Use Committee (IACUC protocol number 2013-097 and 2015-0038). No animals were euthanized for this study. CONSENT FOR PUBLICATION: Not applicable COMPETING INTERESTS: The authors declare that they have no competing interest. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Citations

This article has been cited 8 times.
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