Types and Characteristics of Various Stem Cells
We will explain the formation of different types of fertilized egg cite in vivo. In addition, we will describe both multipotent and pluripotent types of stem cells, including tissue stem cells, somatic stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), which are used in regenerative medicine and drug discovery screening.
Process of Individual Formation from embryo
A wide variety of cell types make up the human body, which is composed of about 60 trillion cells in total. Each of those cells is ultimately derived from a single fertilized egg cell, which began to divide, eventually differentiating into the somatic cells of different morphology and function that form the various tissues and organs of the human body. Pluripotent stem cells are considered to have similar potential without extraembryonic differentiation.
Figure: Induction of the various tissue cell types from pluripotent stem cells via three germ layers
In the process of forming an individual, the stem cells change (differentiate) into cells that are different from themselves while retaining the proliferation ability to divide and create more cells of the same type, or further differentiate into a more specialized form. This is how various organs are created.
In the blastocyst stage, an early stage of embryonic development, there are cells that are capable of differentiating into almost any cell type that makes up the body, an ability known as pluripotentcy. In vitro, pluripotent stem cells including ES cells and iPS cells can differentiate into the cell types derived from the endoderm, mesoderm, and ectoderm, but are not capable of developing into a complete organism alone. By contrast, stem cells that can only differentiate into a limited number of cell types, such as tissue stem cells and somatic stem cells, are known as multipotent stem cells.
These cells are used not only for basic research, where they are differentiated into specific cells to examine their properties, but also for "drug discovery screening" to search for drug candidates, and "regenerative medicine" where they are transplanted or administered to patients as the therapeutic agent. However, culture of pluripotent stem cells is different from conventional somatic cell culture in many ways, and it is said to be difficult to maintain the undifferentiated state and ensure a high level of reproducibility.
Classification and Characteristics of Multipotent Stem Cells and Pluripotent Stem Cells [Multipotent Stem Cells]
Multipotent Stem Cells
Multipotent stem cells have the ability to differentiate into cells that comprise specific tissues and organs, and includes both tissue stem cells and somatic stem cells.
Tissue stem cells are tissue-specific, and have the ability to either self-renew by division into daughter cells of like type or to differentiate into more specialized cells within the tissue.
Somatic stem cells exist in vivo and can differentiate into a limited number of cell types. Mesenchymal stem cells (MSCs), are a type of somatic stem cell, and can differentiate into bone, cartilage, blood vessels, and cardiomyocytes. MSCs are obtained with relative ease from bone marrow, umbilical cord tissue, umbilical cord blood, and adipose tissue.
Multipotent stem cells are reported to have an anti-inflammatory effect, a growth factor-inducing effect, a proangiogenic effect, and to play an important role in tissue repair. Additionally, they are said to have reduced risk of canceration compared to pluripotent stem cells, an important safety consideration.
Regenerative medical products have already been approved worldwide for the treatment of spinal cord injury and post hematopoietic stem cell transplantation acute graft-versus-host disease1).
Table: Examples of Approved Regenerative Medical Products That Use Human MSCs in the World1~6)
| Regenerative Medical Products | Approved Countries | Manufacturing Distributors | Origin MSC | Applications |
|---|---|---|---|---|
| PROCHYMAL® | Canada, New Zealand | Mesoblast | Allogeneic bone marrow-derived MSC | Acute GVHD*(pediatric) |
| TEMCELL® HS Inj. | Japan | JCR Pharma | Allogeneic bone marrow-derived MSC | Acute GVHD* |
| Stemirac® Inj. | Japan (conditional approval) | Nipro | Autologous bone marrow-derived MSC | Spinal cord injury |
| Heartcellgram-AMI® | South Korea | Pharmicell | Autologous bone marrow-derived MSC | Acute myocardial infarction |
| Cupistem® | South Korea | Anterogen | MSC derived from own fat | Crohn's disease |
| CARTISTEM® | South Korea, EU | Medipost | Allogeneic cord blood-derived MSC | Knee osteoarthritis |
| Stempeucel® | EU, India (conditional approval) |
Stempeutics Research |
Allogeneic bone marrow-derived MSC | Knee osteoarthritis |
| Allostem® | USA | Allosource | Allogeneic fat derived MSC (A combination product composed of human demineralized bone matrix) |
Bone damage |
| Osteocel® Plus | US | NuVasive | Allogeneic bone marrow-derived MSC (A combination product composed of osteoprogenitor cells and human demineralized bone matrix) |
Bone repair (361HCT/P) |
*GVHD: Graft Versus Host Disease
Pluripotent stem cells
Pluripotent stem cells are stem cells that can differentiate into almost any cell that makes up the body. ESCs, embryonic germ cells (EGCs), and iPSCs have so far been established as types of pluripotent stem cells.
ESCs are established from the inner cell mass inside the hollow blastocyst, which is an early stage of embryonic development following division by the zygote into a blastula. In Japan, ES cells are established from the surplus supply of fertilized eggs that are discarded following infertility treatment. EGCs are developed from the cellular precursors of sperm and eggs (primordial germ cells) and have almost the same properties as ESCs.
iPSCs are created by reprogramming somatic cells to an undifferentiated state through the introduction of specific genes. The establishment of iPSCs has enabled us to obtain cells similar to ESCs from donors. It is also possible to get tissue supplied by a patient with a disease, establish iPSCs from the tissue, and induce differentiation to provide an in vitro model of the disease. Therefore, somatic cells, such as nerve cells or cardiomyocytes, created by induced differentiation of iPSCs have great potential for applications such as the determination of disease etiology, evaluation of drug efficacy and side effects, and transplantation into patients as regenerative medicine therapies. However, unintended gene mutations have been reported when establishing iPSC cultures, as well as subculturing iPSCs and ESCs over long periods of time7),8). It is unknown at present whether all of these genetic mutations are dangerous, and researchers are discussing how best to evaluate their safety for practical use in the future9).
References
1) Appl Microbiol Biotechnol. 2018; 102(9): 3981-94
2) Cell Tissue Res. 2019; 378(3): 399-410.
3) Spine Res. 2019; 5 (1:2): 1-9
