A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo

Regenerative biological therapies using mesenchymal stem cells (MSCs) are being studied and used extensively in equine veterinary medicine. One of the important properties of MSCs is the cells' reparative effect, which is brought about by paracrine signaling, which results in the release of bio...

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Main Authors: Michael Caruso, Shannon Shuttle, Lisa Amelse, Hoda Elkhenany, James Schumacher, Madhu S. Dhar
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Veterinary Science
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2022.1011905/full
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author Michael Caruso
Shannon Shuttle
Lisa Amelse
Hoda Elkhenany
Hoda Elkhenany
James Schumacher
Madhu S. Dhar
Madhu S. Dhar
author_facet Michael Caruso
Shannon Shuttle
Lisa Amelse
Hoda Elkhenany
Hoda Elkhenany
James Schumacher
Madhu S. Dhar
Madhu S. Dhar
author_sort Michael Caruso
collection DOAJ
description Regenerative biological therapies using mesenchymal stem cells (MSCs) are being studied and used extensively in equine veterinary medicine. One of the important properties of MSCs is the cells' reparative effect, which is brought about by paracrine signaling, which results in the release of biologically active molecules, which in turn, can affect cellular migration and proliferation, thus a huge potential in wound healing. The objective of the current study was to demonstrate the in vitro and in vivo potentials of equine allogenic bone marrow-derived MSCs for wound healing. Equine bone marrow-derived MSCs from one allogenic donor horse were used. Equine MSCs were previously characterized for their in vitro proliferation, expression of cluster-of-differentiation markers, and trilineage differentiation. MSCs were first evaluated for their migration using an in vitro wound healing scratch assay, and subsequently, the conditioned medium was evaluated for their effect on human fibroblast proliferation. Subsequently, allogenic cells were intradermally injected into full-thickness, cutaneous thoracic wounds of 4 horses. Wound healing was assessed by using 3-D digital imaging and by measuring mRNA expression of pro-and anti-inflammatory markers for 30 days. Using human fibroblasts in an in vitro wound healing assay, we demonstrate a significantly higher healing in the presence of conditioned medium collected from proliferating MSCs than in the presence of medium containing fetal bovine serum. The in vitro effect of MSCs did not translate into a detectable effect in vivo. Nonetheless, we proved that molecularly characterized equine allogenic MSCs do not illicit an immunologic response. Investigations using MSCs derived from other sources (adipose tissue, umbilical cord), or a higher number of MSCs or a compromised animal model may be required to prove the efficacy of equine MSCs in wound healing in vivo.
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spelling doaj.art-57b4952c7098433091765d3e25b029fd2022-12-22T03:39:19ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692022-11-01910.3389/fvets.2022.10119051011905A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivoMichael Caruso0Shannon Shuttle1Lisa Amelse2Hoda Elkhenany3Hoda Elkhenany4James Schumacher5Madhu S. Dhar6Madhu S. Dhar7Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United StatesDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United StatesDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United StatesDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United StatesDepartment of Surgery, Faculty of Veterinary Medicine, Alexandria University, Alexandria, EgyptDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United StatesDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Knoxville, TN, United StatesDepartment of Surgery, Faculty of Veterinary Medicine, Alexandria University, Alexandria, EgyptRegenerative biological therapies using mesenchymal stem cells (MSCs) are being studied and used extensively in equine veterinary medicine. One of the important properties of MSCs is the cells' reparative effect, which is brought about by paracrine signaling, which results in the release of biologically active molecules, which in turn, can affect cellular migration and proliferation, thus a huge potential in wound healing. The objective of the current study was to demonstrate the in vitro and in vivo potentials of equine allogenic bone marrow-derived MSCs for wound healing. Equine bone marrow-derived MSCs from one allogenic donor horse were used. Equine MSCs were previously characterized for their in vitro proliferation, expression of cluster-of-differentiation markers, and trilineage differentiation. MSCs were first evaluated for their migration using an in vitro wound healing scratch assay, and subsequently, the conditioned medium was evaluated for their effect on human fibroblast proliferation. Subsequently, allogenic cells were intradermally injected into full-thickness, cutaneous thoracic wounds of 4 horses. Wound healing was assessed by using 3-D digital imaging and by measuring mRNA expression of pro-and anti-inflammatory markers for 30 days. Using human fibroblasts in an in vitro wound healing assay, we demonstrate a significantly higher healing in the presence of conditioned medium collected from proliferating MSCs than in the presence of medium containing fetal bovine serum. The in vitro effect of MSCs did not translate into a detectable effect in vivo. Nonetheless, we proved that molecularly characterized equine allogenic MSCs do not illicit an immunologic response. Investigations using MSCs derived from other sources (adipose tissue, umbilical cord), or a higher number of MSCs or a compromised animal model may be required to prove the efficacy of equine MSCs in wound healing in vivo.https://www.frontiersin.org/articles/10.3389/fvets.2022.1011905/fullhorsemesenchymal stem cellswound healingbone marrowallogenic cellsthoracic wounds
spellingShingle Michael Caruso
Shannon Shuttle
Lisa Amelse
Hoda Elkhenany
Hoda Elkhenany
James Schumacher
Madhu S. Dhar
Madhu S. Dhar
A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo
Frontiers in Veterinary Science
horse
mesenchymal stem cells
wound healing
bone marrow
allogenic cells
thoracic wounds
title A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo
title_full A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo
title_fullStr A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo
title_full_unstemmed A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo
title_short A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo
title_sort pilot study to demonstrate the paracrine effect of equine adult allogenic mesenchymal stem cells in vitro with a potential for healing of experimentally created equine thoracic wounds in vivo
topic horse
mesenchymal stem cells
wound healing
bone marrow
allogenic cells
thoracic wounds
url https://www.frontiersin.org/articles/10.3389/fvets.2022.1011905/full
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