What is Cellular Therapy?
Cellular therapy is one of the subfields of regenerative medicine that focuses on replacing diseased cells with healthy ones. It involves delivering the stem cells to the area of damage or disease.
V-cell therapy uses very small embryonic-like stem cells (VSELs). V-cells are a blood-forming cell that is only found in your bone marrow.
Virus-Specific T-Cell Therapy (VST)
People with healthy immune systems are exposed to viruses at some point in their lives. Typically, the virus “stays asleep” inside them, but for transplant recipients with severe T-cell deficiency, these viruses can awaken and cause life-threatening complications. VST therapy is a way to treat these infections.
Virus-specific T-cells (VST) have been shown to be safe and effective in patients post-HSCT for treatment or prevention of CMV, EBV, and adenovirus (AVD). VST can also be used for prophylaxis before HSCT in people with severe T-cell deficiency.
Researchers are making banks of virus-specific T cells that can be used to treat different infections. They are evaluating the best ways to produce these cells in the lab, and how to use them for treatment in patients. The cells can be donor-derived, or made by a third party, and they can target specific viruses like adenovirus, cMV, or EBV. They can also be made to target multiple viruses at once.
When Yamanaka et al first published that they could reprogramme human somatic cells into pluripotent stem cells in February 2009, laboratories around the world rushed to apply the technique. It was quickly shown that high levels of expression of the four factors Oct3/4, Sox2, Klf4 and c-Myc can reprogram fibroblast cells to iPS cells, which are the same type of stem cell that is found in embryos.
These cells are promising for regenerative medicine because they are autologous, meaning they come from the patient, avoiding immune rejection. Scientists have already used iPS cells to create organoids, including mini-guts and mini-liver, and to recapitulate a number of disease-related genetic and cellular alterations.
The reprogramming of nonpluripotent cells to iPS cells can be accomplished in many ways, such as expression plasmids or delivery via retro or lentiviral vectors that integrate into the target cell’s genome. Recently, it has been possible to use adenoviral vectors that avoid integration into the genome and work with the cell cytoplasm to induce expression of pluripotency factors.
Autologous cell therapies are made from cells and tissues from the patient being treated, for example bone marrow and cord blood stem cells. The advantage of autologous therapy is that it is unlikely to be rejected by the body’s immune system and therefore more likely to “take”, or engraft, into the body.
However, the manufacture of autologous therapy requires a separate procedure for extracting stem cells from the patient and another procedure for their reintroduction after culture expansion. As a result, the manufacturing process for autologous cell therapy is expected to be much more costly than allogeneic. This is mainly due to the higher processing requirements for quality control (QC), as discussed above, and also due to the fact that a single dose of autologous therapy requires a significant number of cells for QC testing as compared to allogeneic cell therapies which require only a small quantity for QC.
The regenerative V-cell therapy is one of the most exciting forms of cellular medicine. It is aimed at combating viral infections that can occur in immunocompromised people after hematopoietic stem cell transplant (HSCT) and solid organ transplant.
These cells are referred to as VSELs and are pluripotent (can become any type of cell in the body). They do not carry the same ethical concerns associated with human embryonic stem cells.
It is believed that VSELs are a population of primitive BM residing CD45- PSC giving rise to long term repopulating hematopoietic stem cells (HSC). Interestingly, recently a similar population of cells showing similar morphology and markers as purified murine BM-derived VSELs have been identified in human BM. They are rare CD34+Lin-CD38- cells that do not exhibit immediate hematological activity, do not grow in vitro colonies in CFU-S assay and do not radioprotect lethally irradiated mice.
Currently, these rare V-cells can be isolated using a laser technology and then genetically engineered to express an anti-tumor receptor. They are then reintroduced into the patient’s bloodstream to fight off cancerous tumors.