An allogenic therapeutic strategy for canine spinal cord injury using mesenchymal stem cells

Bhat, Irfan Ahmad; Sivanarayanan, T.B.; Somal, Anjali; Pandey, Sriti; Bharti, Mukesh Kumar; Panda, B.; Indu, B; Verma, Megha; Anand, J. C.; Sonwane, Arvind; Kumar, G. Sai; Amarpal,; Chandra, Vikash; Sharma, G. Taru

doi:10.1002/jcp.27086

Cited by 41 publications

(36 citation statements)

References 57 publications

(80 reference statements)

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“…Canine SCI studies employing human UC‐MSCs (J. H. Lee, Chung, et al, ) and canine UC‐MSCs (Besalti et al, ; Lim et al, ; Park et al, ) demonstrated improved scores (Tarlov; the Basso, Beattie, Bresnahan; and Olby scores). Implantation of BM‐MSCs (Bhat et al, ; Penha et al, ) and AD‐MSCs (Park et al, ) also demonstrated improved scores and locomotion in animals. In our own clinical study in spinal cord injured dogs (n‐44), allogenic BM‐MSCs implanted in dogs at 15 days interval showed significantly improved body reflexes and recovery scores (Olby scores) as compared with those dogs managed by the conventional treatment (Bhat et al, ).…”

Section: In Vivo Potential Therapeutic Applicationsmentioning

confidence: 99%

“…Implantation of BM‐MSCs (Bhat et al, ; Penha et al, ) and AD‐MSCs (Park et al, ) also demonstrated improved scores and locomotion in animals. In our own clinical study in spinal cord injured dogs (n‐44), allogenic BM‐MSCs implanted in dogs at 15 days interval showed significantly improved body reflexes and recovery scores (Olby scores) as compared with those dogs managed by the conventional treatment (Bhat et al, ). Besides clinical scores, significantly better histological scores (Lim et al, ; Ryu et al, ) and lower fibrosis (S. H. Lee, Kim, et al, ; Park et al, ; Park et al, ), and fewer cavitations were seen on MRI (Jung et al, ; Lee et al, , J. H. Lee, Chung, et al, ; Lim et al, ) in cell treated groups compared with control/sham groups.…”

Section: In Vivo Potential Therapeutic Applicationsmentioning

confidence: 99%

“…Apart from preclinical models, dMSCs have been applied in canine clinical spinal cord injuries (Bhat et al, 2019;Escalhão et al, 2017;Granger et al, 2012;Kim et al, 2011;J. H. Lee, Chung, et al, 2011;Nishida et al, 2011;Penha et al, 2014;Sarmento et al, 2014) (Bhat et al, 2019). Besides clinical scores, significantly better histological scores (Lim et al, 2007;Ryu et al, 2009) and lower fibrosis (S. H. Park et al, 2011;Park et al, 2012b), and fewer cavitations were seen on MRI (Jung et al, 2009;, J. H. Lee, Chung, et al, 2011Lim et al, 2007) in cell treated groups compared with control/sham groups.…”

Section: Nervous Systemmentioning

confidence: 99%

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Mesenchymal stem cell basic research and applications in dog medicine

Gugjoo

Amarpal

Sharma

2019

Journal Cellular Physiology

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The stem cells, owing to their special characteristics like self‐renewal, multiplication, homing, immunomodulation, anti‐inflammatory, and dedifferentiation are considered to carry an “all‐in‐one‐solution” for diverse clinical problems. However, the limited understanding of cellular physiology currently limits their definitive therapeutic use. Among various stem cell types, currently mesenchymal stem cells are extensively studied for dog clinical applications owing to their readily available sources, easy harvesting, and ability to differentiate both into mesodermal, as well as extramesodermal tissues. The isolated, culture expanded, and characterized cells have been applied both at preclinical as well as clinical settings in dogs with variable but mostly positive results. The results, though positive, are currently inconclusive and demands further intensive research on the properties and their dependence on the applications. Further, numerous clinical conditions of dog resemble to that of human counterparts and thus, if proved rewarding in the former may act as basis of therapy for the latter. The current review throws some light on dog mesenchymal stem cell properties and their potential therapeutic applications.

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Section: In Vivo Potential Therapeutic Applicationsmentioning

confidence: 99%

Section: In Vivo Potential Therapeutic Applicationsmentioning

confidence: 99%

Section: Nervous Systemmentioning

confidence: 99%

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Mesenchymal stem cell basic research and applications in dog medicine

Gugjoo

Amarpal

Sharma

2019

Journal Cellular Physiology

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“…Mesenchymal stem cells (MSCs), which have been isolated from bone marrow, umbilical cord, dental pulp, and a diversity of other tissues, have the ability of differentiating into tissue‐specific lineages . An increasing number of studies have demonstrated promising applications of MSCs in regenerative medicine and tissue engineering to repair and regenerate damaged or lost tissues due to diseases and traumatic injuries and, nonetheless, translational uses of MSCs remain inefficacious, in part due to their limited capability of migrating and homing . Thus, gaining insights into the mechanisms regulating MSC migration can provide useful information for developing novel strategies to prepare MSCs for clinical applications and improve the efficacy of MSC‐based therapies as well as evolving a better understanding of the contentious MSC biology .…”

Section: Introductionmentioning

confidence: 99%

Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling

Mousawi

Peng

et al. 2020

Stem Cells

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In this study, we examined the Ca2+‐permeable Piezo1 channel, a newly identified mechanosensing ion channel, in human dental pulp‐derived mesenchymal stem cells (MSCs) and hypothesized that activation of the Piezo1 channel regulates MSC migration via inducing ATP release and activation of the P2 receptor purinergic signaling. The Piezo1 mRNA and protein were readily detected in hDP‐MSCs from multiple donors and, consistently, brief exposure to Yoda1, the Piezo1 channel‐specific activator, elevated intracellular Ca2+ concentration. Yoda1‐induced Ca2+ response was inhibited by ruthenium red or GsMTx4, two Piezo1 channel inhibitors, and also by Piezo1‐specific siRNA. Brief exposure to Yoda1 also induced ATP release. Persistent exposure to Yoda1 stimulated MSC migration, which was suppressed by Piezo1‐specific siRNA, and also prevented by apyrase, an ATP scavenger, or PPADS, a P2 generic antagonist. Furthermore, stimulation of MSC migration induced by Yoda1 as well as ATP was suppressed by PF431396, a PYK2 kinase inhibitor, or U0126, an inhibitor of the mitogen‐activated protein kinase MEK/ERK signaling pathway. Collectively, these results suggest that activation of the Piezo1 channel stimulates MSC migration via inducing ATP release and subsequent activation of the P2 receptor purinergic signaling and downstream PYK2 and MEK/ERK signaling pathways, thus revealing novel insights into the molecular and signaling mechanisms regulating MSC migration. Such findings provide useful information for evolving a full understanding of MSC migration and homing and developing strategies to improve MSC‐based translational applications.

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“…Treating skin wounds with minimal scar formation is a challenge in humans as well as in veterinary medicine (Jackson, Nesti, & Tuan, 2012). One possible solution is cytotherapy or transplantation of mesenchymal stem cells (MSCs; Bhat et al, 2018). Over the past decade, stem cell‐based regenerative therapy is gaining popularity due to their capacity to renew themselves through mitotic cell division and differentiation into specialized cell types of diverse range (Ilic & Polak, 2011).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell‐conditioned media: A novel alternative of stem cell therapy for quality wound healing

Joseph

Baiju

Bhat

et al. 2020

Journal Cellular Physiology

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Mesenchymal stem cells‐conditioned media (MSCs‐CM) contains several growth factors and cytokines, thus may be used as a better alternative to stem cell therapy, which needs to be elucidated. The present study was conducted to evaluate the therapeutic potential of caprine, canine, and guinea pig bone marrow‐derived MSCs‐CM in excision wound healing in a guinea pig model. MSCs were obtained from bone marrow, expanded ex vivo and characterized as per ISCT criteria. CM was collected assayed by western blot to ascertain the presence of important secretory biomolecules. Quantitative estimation by enzyme‐linked immunosorbent assay was done for a vascular epidermal growth factor (VEGF) and interleukin‐6 (IL‐6) in caprine MSCs‐CM and optimum time for collection of CM was decided as 72 hr. CM from all the species was lyophilized by freeze‐drying method. Full‐thickness (2 × 2 cm2) excision skin wounds were created in guinea pigs (six animals in each group) and respective lyophilized CM mixed with laminin gel was applied topically at weekly interval. On Day 28, histopathological examinations of healed skin were done by hemotoxylin and eosin staining. MSCs were found to secrete important growth factors and cytokines (i.e., VEGF, transforming growth factor‐β1, fibroblast growth factor‐2, insulin‐like growth factor‐1, stem cell factor, and IL‐6) as demonstrated by immunohistochemistry and western blot assay. It was found that allogenic and xenogenic application of CM significantly improved quality wound healing with minimal scar formation. Thus, MSCs‐CM can be used allogenically as well as xenogenically for quality wound healing.

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An allogenic therapeutic strategy for canine spinal cord injury using mesenchymal stem cells

Cited by 41 publications

References 57 publications

Mesenchymal stem cell basic research and applications in dog medicine

Mesenchymal stem cell basic research and applications in dog medicine

Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling

Mesenchymal stem cell‐conditioned media: A novel alternative of stem cell therapy for quality wound healing

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