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BMC veterinary research2016; 12; 65; doi: 10.1186/s12917-016-0692-x

Inflammatory response to the administration of mesenchymal stem cells in an equine experimental model: effect of autologous, and single and repeat doses of pooled allogeneic cells in healthy joints.

Abstract: Mesenchymal stem cells (MSCs) transplantation has become a promising therapeutic choice for musculoskeletal injuries. Joint-related disorders are highly prevalent in horses. Therefore, these animals are considered as suitable models for testing MSC-based therapies for these diseases. The aim of this study was to investigate the clinical and inflammatory responses to intra-articular single and repeat dose administration of autologous or of pooled allogeneic MSCs in healthy equine healthy joints. Six horses were intra-articularly injected with a single autologous dose of bone marrow derived MSCs (BM-MSCs) and two separate doses of allogeneic BM-MSCs pooled from several donors. All contralateral joints were injected with Lactated Ringer's Solution (LRS) as the control vehicle. Signs of synovitis and lameness were evaluated at days 0, 1, 2, 3, 5 and 10 after injection. Total protein (TP), white blood cell count (WBC) and neutrophil count (NC) in synovial fluid were also measured at the same time-points. Results: A mild synovial effusion without associated lameness was observed after all BM-MSCs injections. The second allogeneic injection caused the lowest signs of synovitis. Local temperature slightly increased after all BM-MSCs treatments compared to the controls. TP, WBC and NC in synovial fluids also increased during days 1 to 5 after all BM-MSCs injections. Both, clinical and synovial parameters were progressively normalized and by day 10 post-inoculation appeared indistinguishable from controls. Conclusions: Intra-articular administration of an allogeneic pool of BM-MSCs represents a safe therapeutic strategy to enhance MSCs availability. Importantly, the absence of hypersensitivity response to the second allogeneic BM-MSCs injection validates the use of repeat dose treatments to potentiate the therapeutic benefit of these cells. These results notably contribute to the development of stem cell based therapies for equine and human joint diseases.
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Publication Date: 2016-03-31 PubMed ID: 27029614PubMed Central: PMC4815220DOI: 10.1186/s12917-016-0692-xGoogle 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 study investigates the impact of using different types of mesenchymal stem cell (MSC) transplants in horses, particularly the effects of using a horse’s own cells versus cells from multiple donors, and single versus repeat doses. The results indicate that repeat doses of stem cells from multiple donors caused the least inflammation in the horse’s joints, and recovered to a level indistinguishable from the control group.

Objective and Study Design

  • The goal of the research was to assess the inflammatory and clinical reactions to single and repeat intra-articular doses of either a horse’s own stem cells (autologous) or those pooled from different donors (allogeneic MSCs).
  • The treatment was tested on six horses, who were each injected with a single dose of autologous MSCs and two separate doses of allogenic MSCs.
  • The joints on the other side were injected with Lactated Ringer’s Solution (LRS) as a control.
  • Indicators of inflammation and lameness were monitored at certain intervals post-injection.

Results

  • Overall, mild synovial effusion, an accumulation of fluid in the joint, was noticed after all stem cell treatments. However, this was not accompanied by lameness in the horses.
  • The second allogenic MSC injection resulted in the lowest signs of synovitis, an inflammation of the synovial membrane in the joints.
  • While local temperature did increase slightly after all stem cell treatments, these were not significantly different compared to the results from the control injections.
  • Other indicators of inflammation (including Total protein, White Blood Cell count, and Neutrophil count) increased during the first five days post-injection, but normalized by the 10th day.

Conclusion and Implications

  • Administering a mixed pool of allogenic BM-MSCs appears to be a safe procedure to enhance MSC availability.
  • Importantly, the lack of an adverse immune response to the second dose of allogenic BM-MSCs lends credibility to the use of repeat dose treatments to improve the effectiveness of these cells.
  • This research contributes significantly to the development of stem cell therapies for both horse and human joint diseases by suggesting new strategies for minimizing inflammation and enhancing effectiveness.

Cite This Article

APA
Ardanaz N, Vázquez FJ, Romero A, Remacha AR, Barrachina L, Sanz A, Ranera B, Vitoria A, Albareda J, Prades M, Zaragoza P, Martín-Burriel I, Rodellar C. (2016). Inflammatory response to the administration of mesenchymal stem cells in an equine experimental model: effect of autologous, and single and repeat doses of pooled allogeneic cells in healthy joints. BMC Vet Res, 12, 65. https://doi.org/10.1186/s12917-016-0692-x

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 12
Pages: 65
PII: 65

Researcher Affiliations

Ardanaz, N
  • Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Vázquez, F J
  • Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Romero, A
  • Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Remacha, A R
  • Laboratorio de Genética Bioquímica LAGENBIO, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Barrachina, L
  • Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
  • Laboratorio de Genética Bioquímica LAGENBIO, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Sanz, A
  • Laboratorio de Genética Bioquímica LAGENBIO, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Ranera, B
  • Laboratorio de Genética Bioquímica LAGENBIO, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Vitoria, A
  • Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Albareda, J
  • Departamento de Cirugía Ortopédica y Traumatología, Hospital Universitario Lozano Blesa, Universidad de Zaragoza, San Juan Bosco, 15, Zaragoza, 50009, Spain.
Prades, M
  • Departament de Medicina i Cirugia Animal, Universidad Autónoma de Barcelona, Edifici H, UAB, 08193 Bellaterra, Barcelona, Spain.
Zaragoza, P
  • Laboratorio de Genética Bioquímica LAGENBIO, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Martín-Burriel, I
  • Laboratorio de Genética Bioquímica LAGENBIO, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain.
Rodellar, C
  • Laboratorio de Genética Bioquímica LAGENBIO, Universidad de Zaragoza, C/Miguel Servet, 177, Zaragoza, 50013, Spain. rodellar@unizar.es.

MeSH Terms

  • Animals
  • Disease Models, Animal
  • Horses
  • Injections, Intra-Articular / adverse effects
  • Injections, Intra-Articular / standards
  • Joint Diseases / therapy
  • Lameness, Animal / etiology
  • Leukocyte Count
  • Mesenchymal Stem Cell Transplantation / standards
  • Neutrophils / physiology
  • Random Allocation
  • Reproducibility of Results
  • Synovial Fluid / cytology
  • Synovitis / etiology

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