Manufacture and Quality Control of Human Umbilical Cord-Derived Mesenchymal Stem Cell Sheets for Clinical Use

Abstract

Human umbilical cord-derived mesenchymal stem cell (UC−MSC) sheets have attracted much attention in cell therapy. However, the culture media and coating matrix used for the preparation of UC−MSC sheets have not been safe enough to comply with current clinical drug standards. Moreover, the UC−MSC sheet preservation systems developed before did not comply with Good Manufacturing Practice (GMP) regulations. In this study, the culture medium and coating matrix were developed for UC−MSC sheet production to comply with clinical drug standards. Additionally, the GMP-compliant preservation solution and method for the UC−MSC sheet were developed. Then, quality standards of the UC−MSC sheet were formulated according to national and international regulations for drugs. Finally, the production process of UC−MSC sheets on a large scale was standardized, and three batches of trial production were conducted and tested to meet the established quality standards. This research provides the possibility for clinical trials of UC−MSC sheet products in the development stage of new drugs and lays the foundation for industrial large-scale production after the new drug is launched.

Evaluation of safety and efficacy of amniotic mesenchymal stem cells for POI in animals

“…Above studies could lay the foundation for cell drug clinical trials, and the results suggested that the hAMSCs preparations might be a safe and effective candidate drug for POI treatment [19] .…”

High-Strength Cell Sheets and Vigorous Hydrogels from Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells

“…Animal studies have consistently demonstrated the therapeutic efficacy of MSC-derived CSs in various conditions, including myocardial ischemia-reperfusion, cartilage injury, bone defects, and corneal regeneration. ,,,− The clinical application of primary MSCs derived from the umbilical cord, bone marrow, or adipose tissue has faced significant challenges due to issues such as donor heterogeneity, limited cell numbers, and batch-to-batch variability. Compared with UCMSCs, IMRCs displayed smaller size, higher cell viability, more powerful immunomodulation, and stronger ECM regulation .…”

“…The first CS was reported in 1990, which was produced on a temperature-responsive culture dish . To improve operability and stability, various methodologies have been implemented, including temperature-responsive, electrical-responsive, photo-responsive, pH-responsive, mechanical, and magnetic systems. − By applying CS technology in tissue engineering reconstruction, it offers a means to circumvent the limitations associated with the utilization of biodegradable scaffolds or single-cell suspension injection.…”

Establishment of reference measurement procedure and reference material for Treponema pallidum

“…The developed dPCR methods and TP RM were applied to a simulated stem cell matrix to assess whether the matrix would affect the sensitivity of dPCR. Based on previous research experience, 25 the culture matrix for stem cells was formulated. The sensitivity of dPCR was verified by selecting TP RM and human genomic DNA quantitative RM (NIM-RM4035-1) and mixing them in accordance with the ratio of initial syphilis, secondary syphilis, latent syphilis and neurosyphilis viral titers at ratios of 1 : 16, 1 : 32, 1 : 64, respectively.…”