What does the future hold for potential stem cell treatments?

Leslie Lee (WHS)

The continuous stream of new discoveries in the field of stem cell research foreshows the dormant strength stem cell holds. It has a potential in becoming a major role-player in a number of medical procedures including xenotransplantation, in a not so distant future. An escalating number of investments and various researches in this subject are making this happen even faster. The stem cell treatment lies at the core of regenerative medicine- a branch of medicine centring on engineering, replacing or regenerating cells, tissues or organs of human, with an aim to restore or establish normal function. Ongoing studies in this subject are unravelling potential ground-breaking treatments in a number of areas which was unthinkable a few decades ago. The two properties of stem cell characteristics are self-renewal and multi-differentiative potential. This implies that it has an ability to undergo a number of cell division cycles yet maintains its undifferentiated state, and to generate into various distinct specialised cell types. There are 4 types of stem cells, which are: • Embryonic stem cells - from the embryo with 3 to 5 days of age. • Adult stem cells - from adults’ bone marrow or fat. • Induced pluripotent stem cells - adult cell genetically programmed into stem cells. • Perinatal stem cells - from amniotic fluid and umbilical cord blood. In order to maintain its self-renewal quality, stem cells undergo special type of divisions, symmetric and asymmetric cell division. Symmetric division results in two identical stem cells, whilst asymmetric cell division gives rise to one stem cell and one progenitor cell. Progenitor cell lies at the centre between a stem cell and fully differentiated cell. They are oligopotent or unipotent, only having the capacity to differentiate into a few or only one cell type, being limited in maintaining self-renewal property. Stem cells are either totipotent, pluripotent or multipotent, indicating that they can self-renew by division to develop into unlimited, or at least multiple specialised cell types present in a specific tissue or organ. Asymmetric division fulfils both roles of self-renewal and differentiation with a single division. However, it only produces one self-renewable stem cell per division, limiting its expansion in number. Symmetric stem cell divisions commonly take place during healing of injury and regeneration. Some adult stem cells seem to divide asymmetrically under steady-state conditions, however, they have the ability to undergo symmetrical division to restore stem cell pools depleted by injury or disease. This capacity to shift between symmetrical and asymmetrical cell division depends on developmental and environmental stimuli, and such act of switching back and forth has been observed in the nervous and hematopoietic systems. Whether the cell division is symmetrical or asymmetrical, the only two possible daughter cells are a stem cell with self-renewal ability and progenitor cell. Although progenitor cell is far closer to a differentiated state, both stem cells and progenitor cells have a function of recovery of damaged tissues, the difference being the level of detail. Because stem cells have its ability to differentiate to any cell type, it can easily replace a wider range of dead or damaged tissue, therefore acting as a mechanism for renewal. This opens the door to a number of treatments, where some are widely in use today. One of the large-scale use in stem cell is a bone marrow transplant, which is widely used to treat Leukaemiasomatic stem cell therapy. Leukaemia is a cancer of white blood cells and to treat this, the procedure involves the replacement of abnormal leukocytes with new leukocytes. Chemotherapy is often used to kill the abnormal leukocytes; however, it is often the case when it does not prove to be enough. Bone marrow transplant from a matching donor allows the stem cell to differentiate into leukocytes. After killing all abnormal leukocytes by radiation and chemotherapy, the donor’s bone marrow is introduced to the bloodstream where they differentiate to healthy leukocytes. Alongside, a similar procedure is widely used to treat sickle cell anaemia, as well as many blood cancers and immune disorders, having to save a number of lives. More than 26,000 patients are treated with blood stem cells in Europe each year, empathizing the big role stem cell plays in the area of medicine. Recent studies using stem cells are revealing a number of fascinating discoveries, where one of them includes a study which consisted of turning stem cells into insulin-producing cells, which could be a life-changing treatment for diabetics in the future. In February of 2019, researchers in the UCSF (University of California San Francisco) transformed human stem cells into ones that produce insulin, a huge discovery in the study of type 1 diabetics. This research can be further expanded into medical procedures such as islet cell transplantation- possibly becoming an alternative to insulin injections. During the research, the team artificially isolated the pancreatic stem cells from the remainder of the pancreas, then regenerated them into groups of insulinproducing cells. As a result, beta cells responded to blood glucose following the transplantation, starting to produce insulin in a similar way to the animal’s own islets within days.

“We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes,” - Matthias Hebrok, PhD, Professor in Diabetes Research at UCSF and director of the UCSF Diabetes Centre.

Another research was conducted from Washington University School of Medicine in St. Louis, MO, on January 2019, on a similar subject. The research team managed to produce beta cells that are more responsive to blood glucose level, where previously it was challenging in regulating the amount of insulin produced from beta cells. The researchers observed that after transplanting the new cells into mice which could not produce insulin, the cells began to secrete the hormone within a few days, as well as helping to control animals’ blood sugar level for several months. Being able to generate more than a billion beta cells in a single lab in just a few weeks shows easy mass production if the time comes. Whether this will work well in us humans, is yet unanswered. It is absolutely crucial to develop a means of testing the cells safely in people, as well as clinical trials. Stem cell research is not only on its way to help diabetics but also in curing HIV patients. Recently, a second person is known to be free from the HIV virus after receiving stem cell therapy. March of 2019, a research team led by Ravindra Gupta replaced the white blood cells of the patient with HIV and immune-cell cancer, with the versions which are HIV-resistant, obtained from a donor with a Δ32 mutation in CCR5 gene through bone marrow transplant. CCR5 gene is responsible for coding the receptor protein on the surface of the immune cell targeted to bind by HIV. It restricts the cellular entry of the virus by having the absence of protein coded by the CCR5 gene, therefore, making the immune cells resistant from infection by CCR5-dependent HIV strains. This is very similar to procedure Brown, the first person to be free from HIV, underwent, where it took place a decade ago. However, this time around, the mode of treatment was much less aggressive than Brown’s, as radiotherapy wasn’t involved but instead the patient was given a regimen consisting of chemotherapy alongside a drug that targets cancerous cells. The replication of this procedure suggests that stem cell therapy for making HIV remissive was not a one-off case, but a possible treatment for people with immune-cell cancer alongside HIV. However, for some strains of HIV, the virus enters the cells using CXCR4 alongside CD4, rather than CCR5. This type of HIV strains is associated with drug resistance or might arise if antiretroviral treatment starts later than normal in the course of infection. Also, donor stem cell transplantation is expensive, as well as carrying high risk and requiring intensive effort and concentration. This study might have proved such replication of procedure is possible, but this would only be viable on a small scale and only targets people with both immunecell cancer and HIV. The fascinating discovery we are waiting for will be aimed at a wider population with easier accessibility. Research in stem cell carries high complications. There are many ethical issues surrounding stem cells especially with embryonic stem cell, and many restrictions are placed on funding and use. Frequently updated strict guidelines are crucial at this age where rapid advances in stem cell research are attracting more scientists into this field of regenerative medicine every year. It is one of the fastest growing areas of science with predicted stem cell market size to worth $297 billion by 2022. From tissue engineering to potential treatment for Parkinson’s and Alzheimer’s’, stem cell holds high expectations in the medical world.

Bibliography

https://www.nature.com/articles/d41586-019-00989-y

https://www.ucsf.edu/news/2019/02/413186/ functional-insulin-producing-cells-grown-lab

http://what-when-how.com/stem-cell/division-typessymmetrical-and-asymmetrical-stem-cell/

https://en.wikipedia.org/wiki/Progenitor_cell

https://www.cell.com/stem-cell-reports/fulltext/ S2213-6711(18)30531-9

https://stemcells.nih.gov/info/basics/7.htm

https://www.diabetes.co.uk/news/2019/feb/scientistsmake-breakthrough-by-turning-stem-cells-into-insulinproducing-cells-94739587.html

https://learn.genetics.utah.edu/content/stemcells/ sctoday/