Stem cells are cells that have the unique ability to develop into different cell types. There are 3 main types of stem cells – embryonic stem cells, adult stem cells, and induced pluripotent stem cells.
Quick Overview
The 3 main types of stem cells are:
- Embryonic stem cells – derived from embryos, they can become any cell type
- Adult stem cells – found in tissues in children and adults, they have a more limited ability to differentiate
- Induced pluripotent stem cells – created by reprogramming adult cells into a pluripotent state
Embryonic Stem Cells
Embryonic stem cells (ESCs) are derived from the inner cell mass of the blastocyst, an early stage embryo that is approximately 5 days old. At this stage, the embryo contains about 150-200 cells. ESCs are pluripotent, meaning they can differentiate into any of the over 200 cell types present in the adult body.
ESCs were first isolated from mouse embryos in 1981 by Martin Evans, Matthew Kaufman, and Gail Martin. The first human ESCs were isolated in 1998 by James Thomson and colleagues at the University of Wisconsin-Madison.
The properties that make ESCs promising for cell-based therapies are:
- Pluripotency – ability to become any cell type
- Self-renewal – can replicate indefinitely
- Plasticity – maintain undifferentiated state but can be stimulated to become specialized cells
Potential applications of ESCs include:
- Understanding early human development
- Generating cells and tissues for transplantation, tissue engineering, and regenerative medicine
- Screening and testing new drugs
- Toxicity testing of compounds
However, the use of human ESCs is controversial because extracting the cells destroys the embryo, which some argue constitutes ending human life. Additionally, there are concerns about potential immune rejection if the cells are transplanted into patients.
Derivation of Embryonic Stem Cells
ESCs are derived from the inner cell mass of the blastocyst. Here are the steps involved:
- In vitro fertilization produces an embryo.
- The embryo divides and forms a blastocyst containing 200 cells after 5 days.
- The blastocyst inner cell mass is isolated.
- The inner cell mass is cultured on feeder cells like mouse embryonic fibroblasts.
- Inner cell mass cells differentiate into colonies of ESCs.
- ESC colonies are passaged and expanded.
Characteristics of Embryonic Stem Cells
Key properties of ESCs:
- Express pluripotency markers like OCT4, SOX2, SSEA4
- Long telomeres – no shortening with division
- High telomerase activity – maintains telomere length
- Normal, stable karyotype
- High clonogenicity – single cell forms colony
- Prolonged undifferentiated proliferation
Embryonic Stem Cell Differentiation
ESCs can differentiate into any somatic cell type. This occurs via multiple intermediate progenitor stages. Differentiation is prompted by:
- Removing growth factors like bFGF that maintain pluripotency
- Adding growth factors that promote differentiation into specific lineages
- Culturing ESCs on extracellular matrix proteins
- Overexpressing certain genes
- Coculturing with differentiated cells
ESC differentiation produces cells such as:
- Neurons
- Cardiomyocytes
- Hepatocytes
- Hematopoietic cells
- Chondrocytes
- Osteoblasts
Adult Stem Cells
Adult or somatic stem cells exist in developed tissues and organs in children and adults. They were first isolated from bone marrow and described by Ernest McCulloch and James Till in the 1960s. Adult stem cells are undifferentiated cells that can self-renew and give rise to differentiated progenitor cells that help maintain and repair tissue.
The main roles of adult stem cells are to maintain tissue homeostasis and regenerate damaged tissues. Activated in response to injury, they divide and differentiate into multiple cell types to replace damaged cells.
Compared to ESCs, adult stem cells have a more limited differentiation potential as they tend to produce cell types from their tissue of origin. For example, hematopoietic stem cells generate blood cell types while intestinal stem cells produce intestinal epithelium cells.
Advantages of using adult stem cells for research and therapy include:
- Can be isolated from patient’s own tissue – less immune rejection
- Avoid ethical concerns with using human embryos
- Lower risk of teratoma formation
Disadvantages include:
- Rare population in tissues – difficult to isolate
- Limited proliferative capacity
- Reduced plasticity – cannot become all cell types
Sources of Adult Stem Cells
Adult stem cells have been identified in many tissues including:
- Bone marrow – hematopoietic, mesenchymal, endothelial progenitors
- Adipose tissue – mesenchymal stem cells
- Brain – neural stem cells
- Intestine – intestinal stem cells
- Liver – hepatic stem cells
- Skeletal muscle – muscle satellite cells
- Skin – epidermal stem cells, melanocyte stem cells
Umbilical cord blood is also a rich source of adult stem cells such as hematopoietic stem cells.
Adult Stem Cell Differentiation
The differentiation potential of adult stem cells varies by cell type but is generally more limited compared to embryonic stem cells. Differentiation is regulated by signals within the stem cell niche.
For example:
- Hematopoietic stem cells form all blood cell types like lymphocytes, erythrocytes, and neutrophils
- Mesenchymal stem cells form bone, cartilage, fat, and muscle cells
- Neural stem cells form neurons, astrocytes, and oligodendrocytes
- Intestinal stem cells form enterocytes, paneth cells, and goblet cells
Adult stem cell differentiation is useful for:
- Tissue regeneration
- Cell-based therapies
- Disease modeling
- Drug screening
Induced Pluripotent Stem Cells
Induced pluripotent stem cells (iPSCs) are adult somatic cells that have been reprogrammed back into an embryonic stem cell-like pluripotent state. This breakthrough technique was first reported in 2006 by Shinya Yamanaka and colleagues at Kyoto University.
iPSCs are typically derived by introducing genes that encode critical pluripotency transcription factors like OCT4, SOX2, KLF4, and c-MYC into adult cells such as skin fibroblasts or blood cells. This reprograms the cells into a pluripotent state capable of differentiating into any cell type.
Like ESCs, iPSCs can:
- Proliferate indefinitely
- Express pluripotency markers
- Differentiate into all adult cell types
Advantages of iPSCs include:
- Avoid the ethical issues of ESCs
- Can be derived from patient’s own cells
- Provide better disease modeling as cells have patient’s genetic background
Disadvantages include:
- Risk of mutations from reprogramming process
- Potential tumor formation in vivo
- Incomplete reprogramming can limit differentiation potential
Induced Pluripotent Stem Cell Generation
The steps to generate iPSCs are:
- Obtain somatic cells from patient like skin, blood, urine
- Introduce reprogramming factors (OCT4, SOX2, KLF4, c-MYC) using viral vectors
- Culture cells in ESC medium about 4 weeks until iPSC colonies emerge
- Pick ESC-like iPSC colonies
- Verify pluripotency marker expression and differentiation ability
- Expand and bank reprogrammed iPSCs
Induced Pluripotent Stem Cell Differentiation
Like ESCs, iPSCs can give rise to almost any somatic cell type. This multipotent differentiation potential allows their use for:
- Disease modeling
- Drug screening and toxicity testing
- Tissue engineering
- Cell replacement therapies
Commonly differentiated human iPSC cell types include:
- Cardiomyocytes
- Hepatocytes
- Neurons
- Hematopoietic progenitors
- Chondrocytes
Protocols direct differentiation using growth factors and small molecules towards specific lineages.
Clinical Use of Induced Pluripotent Stem Cells
While still an emerging field, there has been some early clinical progress with iPSC-based therapies:
- In 2014, Masayo Takahashi transplanted iPSC-derived retinal pigment epithelium cells for macular degeneration.
- In 2018, Jun Takahashi transplanted iPSC-derived dopaminergic neurons into a Parkinson’s disease patient.
- Ongoing trials are assessing iPSC-derived cardiomyocytes for heart disease.
Challenges for translation include:
- Risk of tumor formation from undifferentiated cells
- Requirement for large scale production under cGMP conditions
- Need for better differentiation and purification protocols
- Immune rejection of transplanted cells
Comparison of Stem Cell Types
Here is a comparison summary of the three main stem cell types:
| Embryonic Stem Cells | Adult Stem Cells | Induced Pluripotent Stem Cells | |
|---|---|---|---|
| Source | Inner cell mass of blastocyst | Various differentiated tissues | Reprogrammed adult somatic cells |
| Potency | Pluripotent | Multipotent or unipotent | Pluripotent |
| Differentiation Potential | Can become any somatic cell type | Limited; tend to remain within tissue lineage | Can become any somatic cell type |
| Advantages | Pluripotency | Readily available; less tumors | Avoid ethical concerns; patient-specific |
| Disadvantages | Ethical concerns; immune rejection | Limited differentiation potential | Mutations; incomplete reprogramming |
Conclusion
The three main types of stem cells are embryonic stem cells, adult stem cells, and induced pluripotent stem cells. Each has unique advantages and disadvantages for research and clinical applications. Further advances in stem cell biology and regenerative medicine will rely on understanding the potential and limitations of these diverse stem cell types.
