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Frontiers in veterinary science2016; 3; 56; doi: 10.3389/fvets.2016.00056

Response to Intravenous Allogeneic Equine Cord Blood-Derived Mesenchymal Stromal Cells Administered from Chilled or Frozen State in Serum and Protein-Free Media.

Abstract: Equine mesenchymal stromal cells (MSC) are commonly transported, chilled or frozen, to veterinary clinics. These MSC must remain viable and minimally affected by culture, transport, or injection processes. The safety of two carrier solutions developed for optimal viability and excipient use were evaluated in ponies, with and without allogeneic cord blood-derived (CB) MSC. We hypothesized that neither the carrier solutions nor CB-MSC would elicit measurable changes in clinical, hematological, or biochemical parameters. In nine ponies (study 1), a bolus of HypoThermosol(®) FRS (HTS-FRS), CryoStor(®) CS10 (CS10), or saline was injected IV (n = 3/treatment). Study 2, following a 1-week washout period, 5 × 10(7) pooled allogeneic CB-MSCs were administered IV in HTS-FRS following 24 h simulated chilled transport. Study 3, following another 1-week washout period 5 × 10(7) pooled allogeneic CB-MSCs were administered IV in CS10 immediately after thawing. Nine ponies received CB-MSCs in study 2 and 3, and three ponies received the cell carrier media without cells. CB-MSCs were pooled in equal numbers from five unrelated donors. In all studies, ponies were monitored with physical examination, and blood collection for 7 days following injection. CD4 and CD8 lymphocyte populations were also evaluated in each blood sample. In all three studies, physical exam, complete blood cell count, serum biochemistry, and coagulation panel did not deviate from established normal ranges. Proportions of CD4(+) and CD8(+) lymphocytes increased at 168 h postinjection in CB-MSC treatment groups regardless of the carrier solution. Decreases in CD4(+/)CD8(+) double positive populations were observed at 24 and 72 h in CB-MSC-treated animals. There was no difference in viability between CB-MSCs suspended in HTS-FRS and CS10. HTS-FRS and CS10 used for low volume excipient injection of MSC suspensions were not associated with short-term adverse reactions. HTS-FRS and CS10 both adequately maintain CB-MSC viability following hypothermic or frozen simulated transport, respectively. CB-MSCs do not elicit clinical abnormalities, but allogeneic stimulation of CD4(+) and CD8(+) lymphocyte populations may occur. Future studies should include in vitro or in vivo evaluation of cell-mediated or adaptive immunity to autologous, identical allogeneic, or MSC originating from additional unrelated individuals in order to better characterize this response.
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Publication Date: 2016-07-22 PubMed ID: 27500136PubMed Central: PMC4956649DOI: 10.3389/fvets.2016.00056Google Scholar: Lookup
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  • Journal Article

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.

The research paper examines the effects of two carrier solutions on equine mesenchymal stromal cells (MSC), which are frequently transported to veterinary clinics in chilled or frozen states. The study tests the safety and efficacy of preserving MSC’s viability during this process and concludes that the two solutions, in conjunction with cord blood-derived (CB) MSC, bring no noticeable alterations in clinical, hematological or biochemical factors in ponies.

Methods

  • The research involved two studies, each with nine ponies as subjects. In the first study, each pony was injected with one of three solutions: HypoThermosol(®) FRS (HTS-FRS), CryoStor(®) CS10 (CS10), or saline, which served as control.
  • In the second study, after a one-week gap, an allogenic CB-MSC was given to the ponies intravenously along with HTS-FRS after a 24-hour simulated chilled transport.
  • A third study involved injecting another pool of allogenic CB-MSC in ponies, with CS10 as the carrier immediately after thawing, following another one-week washout period.
  • The CB-MSCs used were pooled equally from five unrelated donors. The ponies’ physical conditions were monitored, and blood samples were collected for a week post-injection. The lymphocyte populations in the blood samples were also studied.

Results

  • The observations from all three studies showed that the ponies’ physical, blood cell count, serum biochemistry, and coagulation panel measurements did not stray from the normal range after receiving the carrier solutions or the CB-MSC.
  • Alterations in lymphocyte populations, specifically CD4(+) and CD8(+), were noticed 168 hours after the ponies were injected with the CB-MSC treatment, regardless of the carrier solution used.
  • The study also found decreases in the population of double positive CD4(+)CD8(+) lymphocytes 24 and 72 hours after CB-MSC treatment.
  • There were no observable differences in viability between CB-MSCs carried by HTS-FRS and those carried by CS10.

Conclusions and Future Directions

  • The study concluded that neither HTS-FRS nor CS10 resulted in short-term adverse reactions when used for the low-volume injection of MSC suspensions.
  • Both carrier solutions were able to preserve the viability of CB-MSCs following hypothermic or frozen simulated transport.
  • However, CB-MSCs may stimulate allogeneic responses in CD4(+) and CD8(+) lymphocyte populations.
  • In anticipation of future research, the study suggests examining cell-mediated or adaptive immunity to autologous, identical allogeneic, or MSC originating from additional unrelated individuals to better understand the observed responses.

Cite This Article

APA
Williams LB, Co C, Koenig JB, Tse C, Lindsay E, Koch TG. (2016). Response to Intravenous Allogeneic Equine Cord Blood-Derived Mesenchymal Stromal Cells Administered from Chilled or Frozen State in Serum and Protein-Free Media. Front Vet Sci, 3, 56. https://doi.org/10.3389/fvets.2016.00056

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 3
Pages: 56
PII: 56

Researcher Affiliations

Williams, Lynn B
  • Department of Biomedical Sciences, University of Guelph , Guelph, ON , Canada.
Co, Carmon
  • Department of Biomedical Sciences, University of Guelph , Guelph, ON , Canada.
Koenig, Judith B
  • Department of Clinical Studies, Ontario Veterinary College, University of Guelph , Guelph, ON , Canada.
Tse, Crystal
  • Department of Biomedical Sciences, University of Guelph , Guelph, ON , Canada.
Lindsay, Emily
  • Department of Biomedical Sciences, University of Guelph , Guelph, ON , Canada.
Koch, Thomas G
  • Department of Biomedical Sciences, University of Guelph , Guelph, ON , Canada.

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This article has been cited 13 times.
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