Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies

Stem Cell Research & Therapy

Steven W Dow¹  Lauren M Habenicht²  Tracy L Webb²  Jessica M Quimby² 

[1]Department of Microbiology, Immunology, and Pathology, Center for Immune and Regenerative Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA

[2]Department of Clinical Sciences, Immunology, and Pathology, Center for Immune and Regenerative Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA

关键词: Urine;    Mesenchymal stem cells;    Kidney;    Feline;    Cytokines;    Cell culture;   

Others  :  847552
DOI  :  10.1186/scrt198

 received in 2012-08-09, accepted in 2013-04-23,  发布年份 2013

【 摘 要 】

Introduction

Administration of mesenchymal stem cells (MSCs) has been shown to improve renal function in rodent models of chronic kidney disease (CKD), in part by reducing intrarenal inflammation and suppressing fibrosis. CKD in cats is characterized by tubulointerstitial inflammation and fibrosis, and thus treatment with MSCs might improve renal function and urinary markers of inflammation in this disease. Therefore, a series of pilot studies was conducted to assess the safety and efficacy of intravenous administration of allogeneic adipose-derived MSCs (aMSCs) in cats with naturally occurring CKD.

Methods

Cats enrolled in these studies received an intravenous infusion of allogeneic aMSCs every 2 weeks collected from healthy, young, specific pathogen-free cats. Cats in pilot study 1 (six cats) received 2 × 10⁶ cryopreserved aMSCs per infusion, cats in pilot study 2 (five cats) received 4 × 10⁶ cryopreserved aMSCs per infusion, and cats in pilot study 3 (five cats) received 4 × 10⁶ aMSCs cultured from cryopreserved adipose. Serum biochemistry, complete blood count, urinalysis, urine protein, glomerular filtration rate, and urinary cytokine concentrations were monitored during the treatment period. Changes in clinical parameters were compared statistically by means of repeated measures analysis of variance (ANOVA) followed by Bonferroni’s correction.

Results

Cats in pilot study 1 had few adverse effects from the aMSC infusions and there was a statistically significant decrease in serum creatinine concentrations during the study period, however the degree of decrease seems unlikely to be clinically relevant. Adverse effects of the aMSC infusion in cats in pilot study 2 included vomiting (2/5 cats) during infusion and increased respiratory rate and effort (4/5 cats). Cats in pilot study 3 did not experience any adverse side effects. Serum creatinine concentrations and glomerular filtration rates did not change significantly in cats in pilot studies 2 and 3.

Conclusions

Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters.

【 授权许可】

   
2013 Quimby et al.; licensee BioMed Central Ltd.

【 图 表 】

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