Standards of clinical-grade mesenchymal stromal cell preparation and quality control (2020 China Version)

Abstract

Mesenchymal stromal cells (MSCs) including mesenchymal stem cells to potentially differentiate into different tissue lineages widely exist in various tissues. In recent years, the clinical research and application of MSCs have become more extensive, but no standardized guidelines for the preparation and quality control of clinical-grade MSCs currently exist. To standardize the preparation and quality control of MSCs using the human umbilical cord, placenta, bone marrow, and adipose tissue as sample sources for the Chinese Association of Neurorestoratology (CANR; Preparatory) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) member units, this standard is formulated following the T11/CSSCR 001-2017 General Requirements for Stem Cells, Good Manufacturing Practice Pharmaceutical Products (2010 Edition), Pharmacopoeia of the People's Republic of China (2015 Edition), Guiding Principles for Quality Control of Stem Cell Preparations and Preclinical Research (Trial), Code for Cell Banking Facility Quality Management, Sterile Drug Appendix to Pharmaceutical Production Quality Management Regulations, GMP Appendix — Cell Therapy Products (Draft for Comment), The International Society for Cellular Therapy position statement (2006), and Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017). Moreover, this standard includes donor evaluation, sample collection, cell preparation, cell inspection, packaging, labeling, transportation and storage, and quality control. It represents the minimum requirements for clinical-grade mesenchymal stromal cell culture and quality control. Moreover, it will be further optimized following the progress of preclinical and clinical research.

Gingival mesenchymal stem cell‐derived exosomes are immunosuppressive in preventing collagen‐induced arthritis

“…Second, when injected intravenously, less than 1% of GMSC can reach the diseased site, differentiate into functional cells, or play a role through paracrine with the stimulation of the inflammatory microenvironment, while other GMSC especially which embedded in the capillary network of the lung, may have undergone apoptosis, although the apoptotic MSCs may participate in in vivo recipient‐mediated immunomodulation and exert a transient therapeutic effect. 22 , 61 Third, GMSC does not express MHC class Π molecules on the surface and cannot activate CD4 + T cells to trigger immune rejection, so it has low immunogenicity, 62 but GMSC can express a small amount of MHC class I molecules, which allows it to be recognized and killed by CD8 + cells, thereby reducing its number. Therefore, GMSC‐Exo may have higher safety and more advantages in comparison with GMSC for preventing RA.…”

miR-129-5p Promotes Osteogenic Differentiation of BMSCs and Bone Regeneration via Repressing Dkk3

“…They have been widely used in bone regeneration applications due to their self-renewal, osteogenesis capabilities, and low immunogenicity [2]. Like most stem cells, MSCs use several key transcription factors to orchestrate their proliferation and differentiation [3,4]. In addition, more and more epigenetic regulators have been found to be involved in MSC lineage choice.…”

Clinical diagnosis guidelines and neurorestorative treatment for chronic disorders of consciousness (2021 China version)

“…Cell dosage is 1 million per side [60]. Furthermore, autologous bone marrow mesenchymal stromal cells (5 × 10 6 ) were injected through the intrathecal way by lumbar puncture [61].…”