Abstract
BackgroundTo investigate the heterogeneities of human umbilical cord mesenchymal stromal cells (HUCMSCs) derived from different donors and their therapeutic variations when applied to mouse liver fibrosis model.MethodsThe characteristics of HUCMSCs derived from multiple donors were comprehensively analyzed including expressions of surface markers, viability, growth curve, karyotype analysis, tumorigenicity, differentiation potentials, and immune regulation capability. Then, the HUCMSCs with distinct immunomodulatory effects were applied to treat mouse liver fibrosis and their therapeutic effects were observed.ResultsThe HUCMSCs derived from multiple donors kept a high consistency in surface marker expressions, viability, growth curve, and tumorigenicity in nude mice but had robust heterogeneities in differentiation potentials and immune regulations. In addition, three HUCMSC lines applied to mice liver fibrosis model had different therapeutic outcomes, in line with individual immune regulation capability.ConclusionThe HUCMSCs derived from different donors have individual heterogeneity, which potentially lead to distinct therapeutic outcomes in mouse liver fibrosis, indicating we could make use of the donor-variation of MSCs to screen out guaranteed general indicators of MSCs for specific diseases in further stromal cell therapy.
Highlights
To investigate the heterogeneities of human umbilical cord mesenchymal stromal cells (HUCMSCs) derived from different donors and their therapeutic variations when applied to mouse liver fibrosis model
We proposed that Mesenchymal stromal cells (MSCs) with individual heterogeneity could display functional variations when applied to certain disease treatment, by which we could make use of the donor-variation of MSCs to screen out guaranteed general indicators of MSCs for specific diseases in further MSCs therapy
We examine the surface markers of HUCMSCs by flow cytometry (FCM) and the results showed that HUCMSCs from 12 donors stably expressed positive surface markers of CD105, CD90, and CD73 and negative surface markers of CD14, CD34, CD45, CD19, and human leukocyte antigen (HLA)-DR (Fig. 1)
Summary
To investigate the heterogeneities of human umbilical cord mesenchymal stromal cells (HUCMSCs) derived from different donors and their therapeutic variations when applied to mouse liver fibrosis model. Cellular Therapy (ISCT) raised a minimal set of standard to specify MSCs as following: (i) MSCs present plastic adherence in standard culture conditions; (ii) MSCs should positively express surface markers of CD73, CD90, CD105, and negatively express CD14/CD11b, CD34, CD45, CD79α/CD19, and human leukocyte antigen (HLA)-DR; and (iii) MSCs maintains the differentiation potentials of adipocytes, osteoblasts, and chondroblasts in vitro [15]. These criteria of MSCs have been debated ever since and each MSC product is deemed to be unique. MSCs, if considered a CTP in therapeutic use, have a huge challenge to achieve stable and uniform biological characteristics for ensuring safety and effectiveness in patients received MSC treatment
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