Finding meaning: Potential relationship between critical quality attributes of MSC's and their Clinical efficacy in GvHD

Background \u0026 Aim Mesenchymal stromal cells (MSC) display immunomodulatory properties that make them a very attractive tool to treat diseases such as Acute Graft Versus Host Disease (aGVHD). However, although the use of MSC in aGVHD is feasible and safe, its efficacy is completely unpredictable. MSC were first isolated from bone marrow (BM-MSC) but can also be isolated from different tissues such as Wharton\u0027s jelly from Umbilical Cord (WJ-MSC). Indeed WJ-MSC have advantages over BM-MSC for standardization of procedures and large-scale production but equivalence of their immunomodulatory activity is not fully demonstrated. This study seeks to elucidate the relationship between the critical quality attributes of BM-MSC and WJ-MSC and the efficacy in the treatment of aGVHD. Methods, Results \u0026 Conclusion To obtain and process the cells, an approved IND was followed in our GMP-compliant production facilities using BM-MSC\u0027s (PEI 13-081) or WJ-MSC\u0027s (PEI 16-017). Retrospective study of patients of four hospitals of Barcelona area with refractory aGVHD treated with MSC produced at Banc de Sang i Teixits between 2017-2019. We have successfully released 13 clinical-grade batches. Cell viability in all of them was \u003e70% and phenotypic profiling resulted in \u003e95% positivity for the expression of CD73, CD90 and CD105 surface markers. Regarding the HLA-DR- marker, although it was expected to be a negative marker on MSCs, we verified that this expression was highly variable especially in BM-MSC in agreement with our previous observations (Figure 1A). The critical quality attributes for each one of the 13 batches (some of the stock batches have not yet been used in patients) and preliminary results from treated patients are summarized in Figure 1B. Interestingly, no differences were found so far between BM-MSC and WJ-MSC in the clinical response of aGVHD treated patients. Although a comprehensive analysis of the characteristics of MSC may still be needed, it is intriguing that, from our preliminary data, in vitro immunomodulatory capacity of WJ-MSC evaluated by measuring the % of inhibition of PBMNC\u0027s proliferation shown in potency assays does not correlate with MSC\u0027s clinical efficacy. Further work may be needed to understand the mechanisms of apoptosis in clinical grade MSC in line with recent observations made by other authors who have suggested that the response may be mediated by the receptor\u0027s ability to induce MCS\u0027s apoptosis.