Assessment of intravenous adipose-derived allogeneic mesenchymal stem cells for the treatment of feline chronic kidney disease: a randomized, placebo-controlled clinical trial in eight cats

Quimby, Jessica M.; Webb, Tracy L.; Randall, Elissa; Marolf, Angela J.; Valdes-Martinez, Alex; Dow, Steve W.

doi:10.1177/1098612x15576980

Cited by 85 publications

(72 citation statements)

References 25 publications

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“…Cats are a particularly important translational model for a number of diseases that are similar in cats and humans, including FIV (HIV) [61], T cell-mediated oral mucosa inflammation [24], chronic renal failure [29], asthma [25], chronic enteropathy [26], and osteoarthritis. The goal of this work was to profile feline ASCs and directly compare their phenotypic, cellular, and immunomodulatory profiles with human ASCs to deepen our understanding of MSC-based therapies as we move towards mechanism-of-action studies in animals and people.…”

Section: Discussionmentioning

confidence: 99%

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Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome

Clark

Fierro

et al. 2017

Stem Cell Res Ther

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BackgroundAdipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome.MethodsHuman and feline ASCs were evaluated for phenotype, immunomodulatory profile, and transcriptome. Additionally, transwells were used to determine the role of cell-cell contact in ASC-mediated inhibition of lymphocyte proliferation in both humans and cats.ResultsSimilar to human ASCs, feline ASCs were highly proliferative at low passages and fit the minimal criteria of multipotent stem cells including a compatible surface protein phenotype, osteogenic capacity, and normal karyotype. Like ASCs from all species, feline ASCs inhibited mitogen-activated lymphocyte proliferation in vitro, with or without direct ASC-lymphocyte contact. Feline ASCs mimic human ASCs in their mediator secretion pattern, including prostaglandin E2, indoleamine 2,3 dioxygenase, transforming growth factor beta, and interleukin-6, all augmented by interferon gamma secretion by lymphocytes. The transcriptome of three unactivated feline ASC lines were highly similar. Functional analysis of the most highly expressed genes highlighted processes including: 1) the regulation of apoptosis; 2) cell adhesion; 3) response to oxidative stress; and 4) regulation of cell differentiation. Finally, feline ASCs had a similar gene expression profile to noninduced human ASCs.ConclusionsFindings suggest that feline ASCs modulate lymphocyte proliferation using soluble mediators that mirror the human ASC secretion pattern. Uninduced feline ASCs have similar gene expression profiles to uninduced human ASCs, as revealed by transcriptome analysis. These data will help inform clinical trials using cats with naturally occurring diseases as surrogate models for human clinical trials in the regenerative medicine arena.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0528-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…For example, feline chronic gingivostomatitis has a similar T-cell activation phenotype to the human oral inflammatory diseases oral lichen planus, apthous stomatitis, and pemphigus vulgaris [27, 28]. Cats also serve as valuable models for noninflammatory diseases, including chronic renal failure [29, 30]. …”

Section: Introductionmentioning

confidence: 99%

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome

Clark

Fierro

et al. 2017

Stem Cell Res Ther

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“…The few published studies on MSC treatment in cats with CKD have evaluated IV or intrarenal delivery of stem cells . Although safety of MSC treatment was demonstrated repeatedly, improvement in renal function was not a consistent finding.…”

Section: Introductionmentioning

confidence: 93%

Intra‐arterial renal infusion of autologous mesenchymal stem cells for treatment of chronic kidney disease in cats: Phase I clinical trial

Thomson

Berent

Weisse

et al. 2019

Veterinary Internal Medicne

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Background There are no known treatments that halt or reverse chronic kidney disease (CKD) in cats. In rodent models, stem cell treatment has been associated with improvement in renal function parameters, especially when stem cells were delivered intra‐arterially to the kidney. To date, only IV and intrarenal stem cell infusions have been studied in cats with CKD with no clinically relevant improvement noted. Objective To assess the safety and feasibility of intra‐arterial delivery of autologous mesenchymal stem cells (MSC) in stromal vascular fraction (SVF) to the kidney in cats with CKD. Animals Five client‐owned domestic cats with International Renal Interest Society stage III CKD. Methods Prospective cohort study (phase I clinical trial). Adipose tissue was harvested from study animals on day 0. On days 2 and 14, an infusion of MSC in SVF was administered into the renal artery via the femoral or carotid artery using fluoroscopic guidance. Serum creatinine and blood urea nitrogen concentration, plasma iohexol clearance, and quality of life assessments were monitored between days 0 and 90. Results The procedure was performed successfully in all cats. No severe adverse events were observed in any cat during the study period. Conclusions and Clinical Importance Intra‐arterial infusion of MSC into the renal artery in CKD cats was feasible and safe within a 3‐month postoperative period. Efficacy and long‐term safety have yet to be established. This procedure requires careful technique and training.

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“…Likewise, in the rhesus monkey, MSC administration ameliorated AKI induced by cisplatin to some extent but did not reverse established interstitial fibrosis . Autologous AdMSCs have been the primary cell source used in feline preclinical models, but none of the studies have been able to replicate the efficacy reported in rodents . Differences between rodent and feline kidneys certainly explain some of these results, which are discouraging as feline CKD more closely resembles human pathology.…”

Section: Interpreting Reports Of Stem Cell Therapies For Kidney Diseasementioning

confidence: 99%

Concise Reviews: Stem Cells and Kidney Regeneration: An Update

Marcheque

Bussolati

Csete

et al. 2018

Stem Cells Translational Medicine

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Significant progress has been made to advance stem cell products as potential therapies for kidney diseases: various kinds of stem cells can restore renal function in preclinical models of acute and chronic kidney injury. Nonetheless this literature contains contradictory results, and for this reason, we focus this review on reasons for apparent discrepancies in the literature, because they contribute to difficulty in translating renal regenerative therapies. Differences in methodologies used to derive and culture stem cells, even those from the same source, in addition to the lack of standardized renal disease animal models (both acute and chronic), are important considerations underlying contradictory results in the literature. We propose that harmonized rigorous protocols for characterization, handling, and delivery of stem cells in vivo could significantly advance the field, and present details of some suggested approaches to foster translation in the field of renal regeneration. Our goal is to encourage coordination of methodologies (standardization) and long‐lasting collaborations to improve protocols and models to lead to reproducible, interpretable, high‐quality preclinical data. This approach will certainly increase our chance to 1 day offer stem cell therapeutic options for patients with all‐too‐common renal diseases. Stem Cells Translational Medicine 2019;8:82–92

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Assessment of intravenous adipose-derived allogeneic mesenchymal stem cells for the treatment of feline chronic kidney disease: a randomized, placebo-controlled clinical trial in eight cats

Cited by 85 publications

References 25 publications

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome

Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome

Intra‐arterial renal infusion of autologous mesenchymal stem cells for treatment of chronic kidney disease in cats: Phase I clinical trial

Concise Reviews: Stem Cells and Kidney Regeneration: An Update

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