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PloS one2019; 14(3); e0212642; doi: 10.1371/journal.pone.0212642

Peripheral blood-derived mesenchymal stem cells demonstrate immunomodulatory potential for therapeutic use in horses.

Abstract: Previously, we showed that mesenchymal stem cells (MSC) can be mobilized into peripheral blood using electroacupuncture (EA) at acupoints, LI-4, LI-11, GV-14, and GV-20. The purpose of this study was to determine whether EA-mobilized MSC could be harvested and expanded in vitro to be used as an autologous cell therapy in horses. Peripheral blood mononuclear cells (PBMC) isolated from young and aged lame horses (n = 29) showed a marked enrichment for MSCs. MSC were expanded in vitro (n = 25) and administered intravenously at a dose of 50 x 106 (n = 24). Treatment resulted in significant improvement in lameness as assessed by the American Association of Equine Practitioners (AAEP) lameness scale (n = 23). MSCs exhibited immunomodulatory function by inhibition of lymphocyte proliferation and induction of IL-10. Intradermal testing showed no immediate or delayed immune reactions to MSC (1 x 106 to 1 x 104). In this study, we demonstrated an efficient, safe and reproducible method to mobilize and expand, in vitro, MSCs in sufficiently high concentrations for therapeutic administration. We confirm the immunomodulatory function of these cells in vitro. This non-pharmacological and non-surgical strategy for stem cell harvest has a broad range of biomedical applications and represents an improved clinically translatable and economical cell source for humans.
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Publication Date: 2019-03-14 PubMed ID: 30870461PubMed Central: PMC6417789DOI: 10.1371/journal.pone.0212642Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • 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 demonstrates that it’s possible to mobilize, expand, and utilize mesenchymal stem cells (MSCs) from the peripheral blood of horses for therapeutic use, showing significant improvement in lameness. This could open new therapeutic implications and economical means for biomedical applications.

Research Background

  • Research interest existed in the potential therapeutic use of mesenchymal stem cells (MSCs) in horses.
  • Earlier studies had shown that MSCs could be mobilized into the peripheral blood using electroacupuncture (EA) at specific acupoints.

Study Purpose

  • The study aimed to determine if these EA-mobilized MSCs could be harvested, expanded in a lab setting, and used as an autologous cell therapy in horses. Autologous cell therapy refers to the process of re-infusing patient’s own cells after manipulation outside of the body.

Findings

  • A marked enrichment for MSCs was found when peripheral blood mononuclear cells (PBMC) were isolated from both young and aged lame horses.
  • The expanded MSCs were then administered intravenously to the horses and the resulting treatment led to a significant improvement in lameness, as assessed by the American Association of Equine Practitioners (AAEP) lameness scale.
  • The MSCs showed immunomodulatory function, which includes the ability to inhibit lymphocyte proliferation and the induction of the cytokine IL-10, an anti-inflammatory molecule.
  • Intradermal testing showed that there were no immediate or delayed immune reactions to the MSCs.

Implications

  • The finding suggests an efficient, safe and reproducible method to mobilize and expand MSCs in a lab setting in high enough concentrations for therapeutic administration.
  • The results confirmed the immunomodulatory function of the MSCs, which has potential implications for a range of biomedical applications.
  • This non-pharmacological and non-surgical method for harvesting stem cells may be a more clinically translatable and economical cell source compared to previous methods.
  • Given the shared evolutionary heritage between horses and humans, the findings potentially have broad significance for human medicine as well.

Cite This Article

APA
Longhini ALF, Salazar TE, Vieira C, Trinh T, Duan Y, Pay LM, Li Calzi S, Losh M, Johnston NA, Xie H, Kim M, Hunt RJ, Yoder MC, Santoro D, McCarrel TM, Grant MB. (2019). Peripheral blood-derived mesenchymal stem cells demonstrate immunomodulatory potential for therapeutic use in horses. PLoS One, 14(3), e0212642. https://doi.org/10.1371/journal.pone.0212642

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 14
Issue: 3
Pages: e0212642

Researcher Affiliations

Longhini, Ana Leda F
  • Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Salazar, Tatiana E
  • Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Vieira, Cristiano
  • Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Trinh, Thao
  • Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Duan, Yaqian
  • Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Pay, Louise M
  • Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
Li Calzi, Sergio
  • Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Losh, Megan
  • Office of Vice President for Research, Indiana University, School of Medicine IACUC, Indianapolis, Indiana, United States of America.
Johnston, Nancy A
  • Laboratory Animal Resource Center, Indiana University, Indianapolis, Indiana, United States of America.
Xie, Huisheng
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America.
Kim, Minsu
  • Department of Clinical Science, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
Hunt, Robert J
  • Hagyard Equine Medical Institute, Lexington, Kentucky, United States of America.
Yoder, Mervin C
  • Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
Santoro, Domenico
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America.
McCarrel, Taralyn M
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America.
Grant, Maria B
  • Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.

MeSH Terms

  • Animals
  • Cell Proliferation
  • Cell Separation
  • Hematopoietic Stem Cell Mobilization
  • Horses
  • Immunomodulation
  • Lymphocytes / cytology
  • Lymphocytes / immunology
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology
  • Transplantation, Autologous

Grant Funding

  • R01 EY007739 / NEI NIH HHS
  • R01 EY012601 / NEI NIH HHS
  • R01 EY028037 / NEI NIH HHS
  • R01 HL110170 / NHLBI NIH HHS

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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This article has been cited 22 times.
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