Acute toxicity study of Mesenchymal Stromal cells derived from Wharton’s Jelly in mouse by intravenous and subcutaneous route

Abstract

Available online on:15.08.2017@http://ijrdpl.com http://dx.doi.org/10.21276/IJRDPL.227 8-0238.2017.6(5).2748-2756 ABSTRACT:Aim: The present study was to evaluate the acute toxicity of WJ-MSCs in mouse by intravenous and subcutaneous route and to assess their potential for side effects, MLD, MTD and LD 50 . Objectives: Wide ranges of clinical and preclinical trials have suggested exploitation of adult MSCs for the cell-based reparative therapeutic approach; considering pros and cons of embryonic stem cells. However, for the clinical use existing adult stem cells source such as bone marrow, adipose tissue may be detrimental due to invasiveness in the procedure, less number of initial isolation and unsuitability for allogenic transplants. Recently fetal tissues such as Placenta, WJ have attracted as a good stem cell source due to its easy accessibility, ethical safety, immunological tolerance and large number of initial isolation of homogenous population necessary for increasing current market demand. Methods: In present study, we tried to work on complete characterization and up-scaling profiling of cells isolated from WJ, along with assessment of possible toxic effects of these cells when administered in-vivo and optimizing the route of administration with other clinical evaluation been addressed. Results: We confirmed that cells isolated from WJ exhibit morphologically and phenotypically similar properties as MSCs. The animal study also reveled that no mortality, no abnormal clinical signs and no remarkable pathological changes. Conclusion: Our animal toxicity study along with attempted rapid expansion of these cells to meet large clinical demands would allow them to be a lucrative candidate for clinical therapy.

Preclinical assessments of safety and tumorigenicity of very high doses of allogeneic human umbilical cord mesenchymal stem cells

“…As far as we know, this present study is the first to demonstrate that IV administration of hUC-MSCs of up to 40 × 10 6 cells/kg BW in a single dose did not cause clinical sign of toxicity and tumorigenicity in acute, sub-chronic and tumorigenicity studies in healthy BALB/c and immunocompromised B-NDG mice and is the maximum tolerable dose. Similar outcomes have been previously reported with lower doses of hUC-MSCs up to 10 × 10 6 cells/kg BW in a single injection were also safe (Wang et al 2012 ; Kannaiyan et al 2017 ; Chan et al 2022 ; Xu et al 2022 ; Pan et al 2023 ).…”

“…Several animal toxicology studies have been conducted to evaluate the efficacy and safety of MSCs from predominantly bone marrow sources (Rengasamy et al 2016 ; Tayebi et al 2022 ). Safety, toxicity and tumorigenicity studies looking at hUC-MSCs were more limited (Wang et al 2012 ; Kannaiyan et al 2017 ; Chan et al 2022 ; Xu et al 2022 ; Pan et al 2023 ). Chan and co-workers reported that hUC-MSCs infused at a dose of 10 × 10 6 cells/kg BW intravenously on Sprague Dawley rats were considered safe and did not alter the haematological and biochemical as well as histological parameters in animals within the 12-wk study (Chan et al 2022 ).…”