Stem Cell Harvesting excites the scientific community because they can be the “holy grail” of regenerative medicine (by a technique such as therapeutic cloning). More unaffected organs, such as tracheas and bladders, have already been grown and transplanted into patients using adult stem cells.
What are Stem Cells?
Stem cells were first proposed by Alexander Maksimov, a Russian histologist, in 1908. They are unspecialized cells that can self-regenerate indefinitely and give rise to lineages of differentiated mature cells with specialized functions.
This potential of stem cells to divide and differentiate into various cell types other than the ordinary tissues they reside in is known as the stem cell’s plasticity. And, this property of being ‘plasticity’ is a usual feature of fertilized eggs (the zygote), and early embryonic cells (the blastomeres).
A zygote has the highest degree of developmental plasticity and is said to be totipotent, that is, the ability to give rise to all tissues and organs, including the placenta. The level of plasticity decreases in blastomeres and give rise to a limited range of cell types that developed from the three germ layers (ectoderm- the outer, mesoderm – the inner, and endoderm- the inner) and is known as pluripotent.
Although pluripotent stem cells can produce to almost every cell type, they cannot develop into an embryo on its own.
As the cell progress to its development, their potency becomes conclusive and give rise to several different types of specialized cells that can only give rise to other cells of its kind, and is now referred to as multipotent.
For example, hematopoietic stem cells are single multipotent stem cells that can give rise to all the cell types that are typical components of the blood.
When the stem cell differentiates into only a few cells, it is known as oligopotent, e.g., lymphoid or myeloid stem cells. While those stem cells producing only one cell type of their own, but have the ability to self-renewal are known as unipotent, e.g., skin cells.
Properties of Stem Cells
The in vitro study revealed the extraordinary power and versatility of stem cells that
- they can proliferate either symmetrically (allowing the increase of stem cell number) or asymmetrically (for the generation of cells with different properties).
- They can either multiply (progenitors or transit-amplifying cells) or be committed to terminal differentiation. Progenitors and transit-amplifying cells have a limited lifespan and, therefore, can only reconstitute a tissue for a short time when transplanted.
- Their self- renewing and ability to generate any tissue for a lifetime has become the fundamental property for a successful therapy and use in regenerative medicine.
- Adult stem cells are believed to reside in a specific area of each tissue, i.e., a “stem cell niche.”
- Multipotent Mesenchymal Stromal cells (MSCs), a type of adult stem cells residing in several mesenchymal tissues, is an example.
Types of Stem Cells, their Origin, and Functions
There are two significant types of stem cells- embryonic stem cells and adult stem cells.
Embryonic stem cells (ESCs) are totipotent cells derived from an early stage of the embryo, that is, from the inner cell mass (ICM) of a blastocyst. They are capable of differentiating into virtually any cell types of primary tissue layers (ectoderm, mesoderm, and endoderm).
Table 1: Cells Regenerated by Embryonic Stem Cell Differentiation
|
Types of Cell Produced |
Functions |
| Adipocyte | Makes and storage of fat compounds |
| Astrocyte | Glia (glue) cells that give structural and metabolic aid to the neurons |
| Cardiomyocyte | Forms the heart |
| Chondrocyte | Makes the cartilage |
| Dendritic cell | Antigen-presenting cell (APC) of the body immune system |
| Endothelial cell | Forms the inner lining (endothelium) of all blood vessels |
| Hematopoietic cell | Gets differentiate into red and white blood cells |
| Keratinocyte | Forms hair and nails |
| Mast cell | Associated with connective tissue and blood vessels |
| Neuron | Forms the brain, spinal cords, and peripheral nervous system |
| Oligodendrocyte | Myelin sheath forming glia cells of the central nervous system |
| Osteoblast | Give rise to osteocytes |
| Pancreatic islet | Insulin-releasing endocrine cells |
| Smooth muscle | The muscle that lines digestive tract and the blood vessels |
Adult stem cells (ASCs) are differentiated somatic or postnatal stem cells of several mesenchymal tissues that give rise to the types of cells belonging in their tissue. For example, bone marrow-derived stem cells return to the bone marrow, and those derived from neural cells migrate to the brain or spinal cord. ASCs can differentiate representing one or two germ layers.
Table 2: Origin of Adult Stem Cells
| Body Tissues or Organ | Types of stem cells present and functions |
| Brain | Brain-derived stem cells can differentiate into
Three types of nervous tissue – astrocytes, oligodendrocytes, and neurons. Blood-cell precursors |
| Bone marrow | Occur as hematopoietic stem cells, which can give rise to blood cells, and stoma cells. |
| Endothelium | Hemangioblasts stem cell. They can differentiate into blood vessels and cardiomyocytes. |
| Skeletal muscle | Stem cells from these muscles mediate the growth of muscle and may proliferate in response to injury or exercise. |
| Skin | These stem cells are involved in the repair and replacement of all types of skin cells. |
| Digestive system | They are responsible for renewing the epithelial lining of the gut. |
| Liver | Hepatocytes repair liver damage |
As stem cells excite the scientific community because they can be the “holy grail” of regenerative medicine (by a technique such as therapeutic cloning). Simpler organs, such as tracheas and bladders, have already been grown and transplanted into patients using adult stem cells.
Fast track>> Therapeutic cloning is the production of an embryonic stem cell by transferring a diploid nucleus from the patient’s somatic cell into an enucleated egg. The stem cells harvested from the blastocyst developed from the enucleated egg are 100% genetically identical to the patient (except mitochondrial DNA).
While treatment using these adult stem cells is rarely considered controversial, using embryonic stem cells has ethical issues for the dissenters. The reason is that there is no way to remove embryonic stem cells from the ICM of a blastocyst without killing the embryo. However, those in favor believe it is unethical to halt medical research that may yield life-changing treatments for patients.
Partially to get past this legal hurdle, scientists have created another type of stem cells known as induced pluripotent stem cells (iPSCs). iPSCs are stem cells generated by reprogramming adult cells to an embryonic stem cell-like state. The reprograming is achieved by inserting genes important for maintaining the essential properties of ESCs.
Harvesting Stem Cells: Processing and Storage
Stem cell transplantation, a generic term, covers both allogeneic and autologous transplants. And for this purpose, stem cells are harvested from different sites of our body. For allogeneic transplants, hematopoietic stem cells are harvested from the peripheral blood, bone marrow, or umbilical cord blood of a healthy donor (a family member or an unrelated volunteer) matched for HLA type.
Fast track>> Patients with common HLA (Human Leukocyte Antigen) type (for example, identical twins) have a good chance of getting a match and lower morbidity and mortality.
For autologous transplants, stem cells are harvested from patients’ peripheral blood or bone marrow.
Depending on the origin of stem cells, the harvesting process varies. Stem cells from the bone marrow, following an anesthetic process, are removed from the pelvic bones (the iliac crest) with the help of an aspirated needle inserted at different points on the bone.
Harvesting peripheral stem cells from the blood requires no anesthetic process. In this process, a drug, granulocyte colony-stimulating factor (GCSF) is injected subcutaneously. It stimulates the mobilization of more blood stem cells from the bone marrow into the bloodstream.
Apheresis
After a few days of injection, stem cells are isolated from the blood by a process known as apheresis. During this process, blood collected from a vein in one arm is passed along a tube into an apheresis machine (a special type of centrifugation). Stem cells are separated while the blood is returned to the body through the vein in another arm.
With the parents’ consent, harvesting stem cells from the tissues such as placental tissue and umbilical cord vein that sustains natal development represents a safe, non-invasive mode for attaining therapeutically beneficial stem cells. Post-delivery these tissues are discarded as medical waste. The cord blood is harvested through an ‘amniocentesis procedure.’ In this procedure, a 16-gauge needle is inserted through the umbilical cord vein once the placenta has been delivered.
The isolated cells from adults or embryos are cultured on a layer of feeder cells to prevent spontaneous differentiation. The feeder cells provide a favorable substrate for the cells to grow. Injection of freshly isolated stem cells into the recipient would lead to the formation of teratomas.
Therefore, harvested stem cells, before storage or transplantation, are manipulated by enriching with CD34+ cells or purged by removing malignant cells or T lymphocytes, which are central to the process of transplant rejection. CD34+ count has a significant correlation with the fruitful harvest yield.
The homogenous cell product so obtained is cryopreserved once the product passed all quality controls and tests of the presence of any pathogens or contaminants. Cryopreservation will allow long-term storage of stem cells without significant loss of viability, prevent the cells from ice formation and dehydration, reduces the risk of cell injury, and decreases the number of mature blood cells in the graft.
Importance of Stem Cell Harvesting
Harvested stem cells have broad applications in stem cell therapy.
- With some degree of success, stem cells from umbilical cord blood are used for the treatment of stroke, myocardial infarction, and other blood-related disorders.
- Hematopoietic stem cells are used in the treatment of numerous blood-based disorders. Current treatments include exposure to nuclear radiation and transplantation for the treatment of genetic diseases or cancer cells of the blood and blood-forming system.
- Rather than regenerative medicines, adult stem cells are under phase II trials of treating patients suffering from myocardial ischemia, transplanting their own bone marrow stem cells into their heart.
- Bone marrow stem cells have made promising results in regeneration of liver in patients with hepatic malignancies, and growing heart valve using a collagen scaffold.
Stem cells, by their unique regenerative abilities, a lineation of the stem cell’s potentiality for treatment of human diseases is now tangible. With proper documentation of cell’s history, their characterization, and requisite safety and quality control regulation, the coming years will usher new potential of cell-based therapy to the health-care system.
Image Credits:
Featured Image: Stem Cell Harvesting and its Importance
Ph.D. Biotechnology, Manipur India
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