Own (Autologous) and Donated (Allogeneic) Stem Cells for Stem Cell Transplantation Therapy

What is Cell-Based Therapy?

Cell-based therapy is a treatment technique that involves the introduction of a patient’s cells or those derived from a donor to combat diseases and allay certain medical conditions due to the regenerative capacity of these types of cells. Cell-based therapy is based on the ability of stem cells (SCs) to differentiate into cells of different types while also being able to self-replicate and retain their progenitors’ characteristics. This ability of SCs to differentiate, self-replicate, and maintain parent-cell characteristics is known as potency. Hence, the use of terms like totipotent, pluripotent, and multipotent.

Totipotent cells are capable of dividing and differentiating into different embryonic cells (including extra-embryonic ones). Using human development as a case study, zygotes (which are themselves, totipotent) give rise to other daughter’s totipotent cellular entities. As the zygote undergoes division during the days immediately after fertilization, the identical cells that arise from the zygote still retain their totipotency until the blastocyst is formed. This is where differentiation begins to occur in the blastocyst’s inner cell mass, and they become pluripotent.

Pluripotency refers to a cell’s ability to differentiate into any of the endodermal, mesodermal or ectodermal layer cellular entities (but not extra-embryonic ones). As they undergo further differentiation and maturation, they become multipotent. Though multipotent cells can still further differentiate into a few different types, they are, however, lineage-restricted.

There are three types of in vivo SCs based on their origin. They are:

1. Embryonic stem cells (ESCs) are obtained after fertilization from the blastocyst’s inner cell mass. They are pluripotent and give rise to other cellular entities that make up the organism.
2. Fetal stem cells (FSCs). These are derived from fetal tissues and are multipotent. Based on their tissue of origin, they can be termed hematopoietic (capable of generating blood, liver and bone marrow cellular entities), epithelial (generating intestine, pancreatic and liver-associated cellular entities), neural (giving rise to tissues of the brain and spinal cord), endothelial (capable of giving rise to cellular entities of the bone marrow and placenta) and mesenchymal SCs (capable of differentiating into blood, bone marrow, liver, kidney, pancreatic and lung cellular entities).
3. Adult stem cells (ASCs) are also known as somatic SCs and are located throughout various body tissues. Unlike ESCs and FSCs, these multipotent cells can be derived from both infant and adult humans. Even though ASCs are situated in almost every tissue of the human body, their concentration is highest in the bone marrow and adipose tissue. Like FSCs, they can also be termed hematopoietic, epithelial, neural, endothelial, and mesenchymal SCs. The umbilical cord blood and the placenta are another viable sources of adult SCs. Studies suggest that cord blood can potentially be used to treat medical conditions that may develop later in a person’s life.

Stem cell transplantation therapy involves injecting, implanting, or grafting these viable SCs into a patient to cause a therapeutic effect to alleviate conditions like lupus, type 1 diabetes, multiple sclerosis and other neurodegenerative diseases, cancer, rheumatoid arthritis, and more.

Types of  Stem Cell Transplants(SCTs)

Based on the source of these viable cellular materials, there are two major stem cell transplantation types. They are autologous transplants and allogeneic transplants.

Autologous Stem Cell Transplant

The word autologous is derived from “auto,” meaning “self.” In autologous transplantation, the source of the SCs is from the same patient that needs to undergo the therapy. Usually, in an autologous transplant, the SCs of the patient are first harvested from their bone marrow, adipose tissue (fat) or blood, and then cultivated, or if required, the patient undergoes intensive chemotherapy and radiotherapy depending on the disease condition being treated. Finally, the processed SCs are thawed and re-injected into the patient’s body.

Advantages of autologous transplantation

A major advantage of autologous SCT is that the patients get their own SCs back, and the risk of the graft being rejected by their bodies (host-versus-graft reaction) is eliminated. In some cases, it is easier and less costly to start up, unlike allogeneic transplants.

In autologous transplants, there are simpler regulations. Also, embryonic sources and non-donor virus and prion concerns can be avoided. Cellular abnormalities are also avoided with autologous SCT, and it is more preferred for bio-aesthetic applications. There is no need for immuno-suppression and all the risks attached to it. Also, there are less ethical issues with autologous SCT when compared with allogeneic SCT since the SCs are harvested from the patient’s own body. These are some of the reasons why in an autologous vs allogeneic transplant comparison, the autologous option may be preferred.

Disadvantages of autologous transplantation

A disadvantage of autologous transplantation is that already infected cellular entities might be harvested along with the SCs and then later re-injected into the patient’s body. For instance, in cancer treatment, since the patient’s immune system was not able to successfully attack the cancerous cellular entities when the SCs are administered back, they might be able to escape attack from the immune system again. Thus, an autogenic stem cell transplant cannot be used to fight existing cancer cellular entities in the patient’s body since re-injected SCs are derived from the same source.

Also, it usually proves difficult to harvest a large number of SCs from ASCs in this type of transplantation. In an autologous vs allogeneic comparison, patient throughput is usually lower with autologous SCT.

Emergencies are quite difficult to deal with in this transplantation type, and in the event of a processing failure, major treatment delays are inevitable. There is no complete stem cell transplant success guarantee in that there is a possibility that the transplanted SCs will not go into the bone marrow as expected.

Another disadvantage is that it requires the procedure of cell harvesting that may be uncomfortable for the patient and has a risk as any invasive medical procedure.

Allogeneic Stem Cell Transplants

The word allogeneic is obtained from “allo,” meaning “other.”  In this transplantation type, the source of the SCs in an allogeneic stem cell transplant is from another individual other than the patient. In an allogeneic transplant, the SCs are gotten from a stem cell donor or donated tissue such as placenta or Wharton’s jelly.

In the case of hematopoietic stem cell transplantation (HSCT), a close family member is a choice for such a stem cell donation. However, if a good match cannot be found in the patient’s family, a matched unrelated donor (MUD) might be selected from the general public via a national registry. In the case of mesenchymal stem cells (MSCs), there is no evidence of a risk of rejection, even if cells are harvested from donated biomaterial.

Advantages of allogeneic SCT

In treating diseases like cancer, the SCs of the donors produce their immune cells, which could be useful in killing any remaining cancerous cellular entities in the bodies of the stem cell recipients. This is known as the graft-versus-cancer effect. Also, more healthy SCs may be obtained from the donors if needed.

In allogeneic SCT, since SCs are always available (as a result of an increasing number of donors found in registries), it is preferable to handle emergencies. Also, when compared to autologous transplants, it gives room for higher patient throughput. No biopsy consent is needed from patients, which can be very important in the case of an extremely ill patient.

Also, the use of allogeneic stem cells avoids the unpleasant procedure associated with cell sampling, and significantly reduces the treatment time, since the cells have already multiplied to the required number.

Disadvantages of allogeneic SCT

The graft or transplant might be rejected by the patient’s body, which will result in the death of the donated SCs because the immune system of the patient regards the grafted allogeneic cells as foreign. Also, the donor’s cellular immune entities may attack not just cancerous cells in the patient but healthy cellular entities as well. This is known as graft-versus-host disease.

Since immune-suppression is necessary to keep the patient’s immune system in check, the patient is at a high risk of being infected with other infections, which could lead to serious complications and even death. The use of allogeneic SCs also presents more ethical issues when compared to using autogenic SCs.

There are other types of stem cell transplants, which are derivatives of autologous and allogeneic transplantation.

1. Tandem transplant (involves carrying out two autologous transplants in a row).
2. Mini transplant (a form of allogeneic transplant that is also known as non-myeloablative transplant or reduced-intensity conditioning).
3. Syngeneic SCT (an allogeneic transplant for patients with an identical sibling).
4. Half-matched or haploidentical transplant (also allogeneic and used for patients who do not have fully matching family members).
5. Umbilical cord blood transplant.
6. Matched unrelated donor (MUD) transplant.

What Results Can be Expected with Cell-Based Therapy?

The homing, regenerative, and transformative characteristics of SCs make cell-based therapy potentially capable of curing many medical conditions that are associated with cellular pathology since the SCs can replace the damaged cells and stimulate tissue renewal. As more research on cell-based therapy is being done by leading medical centers such as Swiss Medica and others worldwide, SCs can be used to treat different autoimmune, neurodegenerative, cardiovascular, metabolic and eye diseases, cancers and other chronic conditions much more effectively.

Although not all of these breakthroughs have been thoroughly tested using human models, the results are promising. The possibilities that this form of treatment offers are numerous and more diseases that were once thought to be incurable may very well be cured in the nearest future.