The History and the Future of Stem Cell Transplantation and Regenerative Therapy

By Dr Stacy-Lee Sigamoney 8 months ago
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According to the South African Stem Cell Transplantation Society, in the mid 1980’s, haematopoietic (blood cell-forming) stem cell transplantation, principally from bone marrow, started to become established as a common practice at university hospitals in Johannesburg and in Cape Town. [1]

Originally, most stem cell transplantations were autologous (self), however there has been extensive growth in allogeneic (donor) transplantation as well, since the early 1990’s, particularly in Cape Town. [1]

Several transplant groups have been established in the private sector, further increasing the scope of this activity.  Early in the new millennium, extensive recognition emerged of the potential of stem cell transplantation as regenerative, individualised therapy and hence it has continued to expand in the scientific community. [1, 2]

This expansion, included the exploration of different sources of stem cells such as induced pluripotent stem cells (iPSCs) from adipose and other adult tissue; and umbilical stem cells from umbilical cord blood and tissue. These encompass both haematopoietic stem cells (blood cell-forming stem cells) and mesenchymal stem cells (multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts/bone cells, chondrocytes/cartilage cells, myocytes/muscle cells and adipocytes/fat cells). These have been distinguished as a novel approach for individualising cell therapies for appropriate candidates. [2]

Pharmaceutical drug development has saved countless lives, but there are many recalcitrant conditions, where the exclusive use of pharmacological interventions cannot result in curative treatment. [3] Individualised cellular therapy allows for adjustment for a patient-specific profile, in order to achieve best therapeutic results and outcome, where recipient factors and donor factors are considered. [2]

Umbilical cord and tissue stem cells allow for a better matching between the donor and the recipient, in comparison to bone marrow-derived stem cells, especially if the donor and recipient are related. Human Leukocyte Antigens (HLA) are proteins on the surface of cells that determine the tissue type of a person. The immune system uses the HLA’s to differentiate its own cells from that of other (non-self) cells. To successfully receive tissue, from another person, the tissue type has to be the same otherwise the recipient’s system will see it as foreign and it will reject the donated tissue.

HLA typing is done on cord blood at time of stem cell transplant. HLA typing is not required on cord tissue. In an autologous stem cell transplant, there is a 100% chance of matching for cord blood, while there is a 25% chance of matching in siblings. Globally, the first matched cord blood transplant occurred between siblings (a brother and sister) in 1988 to treat Fanconi’s Anaemia, a genetic condition that tends to lead to myeloid leukaemia and bone marrow failure. [4; 5]

Haemoglobinopathy (a blood disorder caused by a genetically-determined alteration in the molecular structure of haemoglobin) testing on cord blood is also endorsed, as there are certain inherited blood-disorders where stem cells cannot be used, as these stem cells have acquired the genetic mutation.

Umbilical cord blood and tissue stem cells have many advantages over other stem cell resources as there are less stringent (HLA) matching requirements than stem cells from other resources, as discussed. Also, the afore-mentioned haemoglobinopathy testing, as well as testing of cell counts and viability are done at the time of stem cell transplantation. Rigorous maternal blood tests and sterility testing are done at birth to test for transmissible diseases that are not routinely done with stem cells from other resources.

There are many ongoing and recently published trials to demonstrate interesting and important concepts and innovations in the field of cord blood and cord tissue banking, transplantation and regenerative medicine. It is acknowledged that variable cell doses are required for particular applications—CD 34-marked stem cell yields can vary dramatically from one collection to another which can influence the potential clinical utility of cord blood units. [6]

One of the challenges of cord blood transplantation is cell dose limitation. There has been substantial interest in ex vivo expansion of umbilical cord blood (UCB) haematopoietic stem cells in order to overcome this problem. In addition, the potential applications of stem cell technologies are constantly expanding and evolving. [6]

Patience and determination are essential to allow the overall completion of objective research and pre-clinical assessment into the safety and efficacy of stem cell transplantation and regenerative therapy into standard practice and application in the clinical environment, as it took half a century to establish bone marrow transplantation from its first attempts to its current level of progress. [3]

In the present, there are controlled clinical trials and epigenetic studies that have already provided the knowledge to distinguish the field of umbilical cord stem cell transplantation and regenerative therapy. [3] There are ongoing trials that can be accessed from this link https://clinicaltrials.gov/, with regards to the use of umbilical stem cells in autologous and/or allogeneic transplantation in the isolated or adjunctive treatment of numerous conditions. There are also multiple clinical trials that have been published on reliable scientific databases such as Pubmed, Ovid and Cochrane to substantiate the importance of the field of umbilical cord and tissue stem cells in different diseases.

There are stem cell transplantation facilities available in South Africa.

The future is to ultimately, achieve the goal of establishing both the safety and efficacy of stem cell therapy, so that it may be practised as the norm in individualised or adjunctive therapy in recalcitrant conditions, as a superior alternative to bone marrow transplantation. [2]

References:

  1. South African Stem Cell Transplantation Society. [Cited 2018 Feb 16] Available from http://www.stemcell.org.za/doctors.htm
  2. Personalized Regenerative Medicine. Arjmand B, Goodarzi P, Mohamadi-Jahani F, et al. Acta Med Iran 2017;55(3):144-149.
  3. Lin H-T, Otsu M, Nakauchi H. 2012 Stem cell therapy: an exercise in patience and prudence. Phil Trans R Soc B 368:20110334. http://dx.doi.org/10.1098/rstb.2011.0334
  4. Canadian Stem Cell Foundation. About Blood Disorders. [Cited 2018 Feb 16] http://stemcellfoundation.ca/en/diseases/blood-disorders/
  5. Ballen K, Gluckman E, Hal E, et al. Umbilical cord blood transplantation: the first 25 years and beyond. Blood. 2013 Jul 25; 122(4): 491–498.Prepublished online 2013 May 14. doi:  1182/blood-2013-02-453175
  6. Smart Cells International. 2017 Sep Newsletter
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 Dr Stacy-Lee Sigamoney

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