General requirements for stem cells

Abstract The standard ‘General requirements for stem cells’ is the first set of general guidelines for stem cell research and production in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the classification, ethical requirements, quality requirements, quality control requirements, detection control requirements and waste disposal requirements of stem cells, which is applicable to stem cell research and production. It was firstly released by the Chinese Society for Cell Biology on 1 August 2017 and was further revised on 30 April 2020. We hope that publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols, and accelerate the international standardization of stem cells for clinical development and therapeutic applications.


| SCOPE
This document specifies the classification, ethical requirements, quality requirements, quality control requirements, detection control requirements and waste disposal requirements of stem cells.
This document is applicable to stem cell research and production.

| TERMS AND DEFINITI ON S
The following terms and definitions apply to this document.

| Ethical committee
A specialized organization responsible for assessing and reviewing ethical issues involved in scientific research.

| Informed consent
The process by which an individual or its designated legal representative voluntarily confirms willingness to donate biological material for research-related purposes, after having been informed of all aspects of the potential research that are relevant for the decision to donate.

| Stem cell
Cells with the capacity for self-renewal, and which can differentiate into one or more different types of specialized functional cells.

| Totipotent stem cell
Stem cells that can differentiate to form a complete and intact new organism.

| Pluripotent stem cell
Stem cells that can self-renew indefinitely in vitro and possess the potential to differentiate into cells of the three embryonic germ layers, namely the endoderm, mesoderm and ectoderm.
Note: Pluripotent stem cells include but are not limited to embryonic stem cells, somatic cell nuclear transfer (SCNT)derived embryonic stem cells, and induced pluripotent stem cells, etc.

| Embryonic stem cell
The primary undifferentiated cells derived from the inner cell mass of a blastocyst or an early-stage pre-implantation embryo that can self-renew indefinitely in vitro and possess the potential to differentiate into cells of the three embryonic germ layers.

| Somatic cell nuclear transfer (SCNT)-derived embryonic stem cell
Embryonic stem cells derived from the inner cell mass of a blastocyst or an embryo produced by the in vitro transfer of a donor somatic cell nucleus into an enucleated oocyte.

| Induced pluripotent stem cell
Pluripotent stem cells similar to embryonic stem cells in properties but which are derived from somatic cells through artificial reprogramming by introducing genes or proteins, or via chemical or drug treatments.

| Adult stem cell
Undifferentiated stem cells located within different adult tissues.

| Harvest
The process of obtaining biological samples such as tissues and/or cells from donors.

| Separation
The process of obtaining target cells from biological samples.

| Cryopreservation
The process by which cells are maintained in an inactive state at a low temperature (<−196°C) so they can be revived later.

| Resuscitation
The process whereby cryopreserved cells return to their normal growth state.

| Expansion
The process of increasing the numbers of cells upon culture.

| Differentiation
The process of gradually converting stem cells into a defined cell state/fate with different morphology and functional characteristics.

| Stem cell bank
A legal entity or part of a legal entity that performs biobanking of different source of stem cells and their associated information.

| Cell purity
The percentage of a particular cell type with defined specific biological characteristics, such as cell surface markers, genetic polymorphisms and biological activities, within a cell population.

| Cell viability
The percentage of cells that are alive and metabolically normal within a cell population.
Note: Cell viability can vary over time in culture and may be measured by metabolic activities (eg, esterase activity, Thiazole blue method based on the determination of succinic dehydrogenase [MTT]), apoptosis markers, cellular redox potential, membrane potential, proliferation rate (eg, DNA content), mitochondrial function and membrane integrity, etc.

| Stem cell self-renewal
The ability of stem cells to divide symmetrically, forming two identical daughter undifferentiated stem cells; or divide asymmetrically, forming one daughter cell which can proceed irreversibly to a differentiated cell lineage and ultimately lead to specialized functional differentiated cells, while the other daughter cell still retains the undifferentiated characteristics of the parental stem cell.

| Stem cell differentiation potential
The ability that stem cells can produce other types of cells with stably different morphologies, structures and biological functions after cell division.

| According to the sources of stem cells
Stem cells can be divided into embryonic stem cells and adult stem cells.

| According to the potential of differentiation
Stem cells can be divided into totipotent stem cells, pluripotent stem cells, multipotent stem cells, oligopotent stem cells and unipotent stem cells.

| General requirements
Appropriate quality control criteria and corresponding methods for establishing stem cell qualities, including biological characteristics, safety, stability and efficacy shall be established and strictly implemented, according to the specific types of stem cells.

| Biological characteristics
Biological characteristics criteria of stem cells shall be established with, including but not limited to gene expression biomarkers, selfrenewal capacity, differentiation potential, cellular morphology, genetics and metabolic isoenzyme activities.

| Safety
Safety criteria of stem cells shall be established with, including but not limited to microbial tests (bacterial, fungal), mycoplasma tests, tests for intra-and extra-cellular pathogenic factors, endotoxin tests, immunological response tests, tumorigenicity tests, tests for residual quantities of culture medium and xenogeneic ingredients.

| Stability
Stability criteria of stem cells shall be established with, including but not limited to the culture density/concentration, purity, viability and biological activities of the stem cells.

| Efficacy
Efficacy criteria of stem cells shall be established with, including but not limited to the expression of specific genes and proteins, the secretion of specific cellular factors, the differentiation potential, as

| Preparation
Harvesting and separation      2. Disqualified/discarded stem cells or their raw source materials (such as the donor's embryo, germ cells, bone marrow, blood, etc.) that arise during stem cell research and production shall be disposed according to legal and/or ethical regulations.