Can liquid glue proliferate hematopoietic stem cells? Is it also expected to reduce the cost of bone marrow transplantation?

Hematopoietic stem cells are tissue stem cells that supply whole body blood cells for life. Hematopoietic stem cells are essential for bone marrow transplantation (hematopoietic stem cell transplantation) to cure blood diseases. Therefore, it is very important to find a suitable donor, but in today's aging society, there are fewer and better donors, and it is urgent to create other auxiliary systems such as the bone marrow bank or the cord blood bank. Therefore, the research team is developing a technique for in vitro culture of hematopoietic stem cells, which is intended to be used in patients with blood diseases/immune diseases including leukemia. Research results
Determine the most appropriate hematopoietic stem cell proliferation factor concentration

This study group previously reported the optimal concentration of induced hematopoietic stem cell division using recombinant protein-based culture conditions. As a result, the balance between the low concentration of SCF and the high concentration of TPO can be effectively cultured for a long period of time while maintaining the properties of hematopoietic stem cells.

1) PVA replaces the function of serum albumin and inhibits cell senescence, thereby proliferating hematopoietic stem cells (Fig. 1)

Purified albumin and recombinant albumin are inevitably mixed with impurities that cannot be removed during the purification process. This study shows that this impurity can induce the differentiation direction of hematopoietic stem cells themselves. It is also known that the oxidation reaction of proteins can induce cell senescence. The team then considered using chemicals instead of albumin instead of other proteins. In the process of solving this problem, the study found that PVA is an effective substitute for albumin. And since PVA is not easily oxidized in the culture solution and is stable in nature, it can maintain long-term cell proliferation while suppressing aging of hematopoietic stem cells.

2) The proliferation culture system of PVA hematopoietic stem cells can even induce the proliferation of cells that can supply multiple receptors from one hematopoietic stem cell.

A hematopoietic stem cell was isolated and extracted from the mouse, and after a month of culture, the radiation was irradiated several times (this step is to destroy the bone marrow-induced anemia) and then transplanted into the mouse. The results confirmed that all proliferating hematopoietic stem cells transplanted into mice were able to undergo bone marrow remodeling. This indicates that a small amount of hematopoietic stem cells derived from the donor can be cultured by proliferation, and even the amount of cells that can be supplied to a plurality of patients can be prepared.

3) Establish a hematopoietic stem cell transplantation model in which the bone marrow is not destroyed safely (Fig. 3)

Many studies have reported that hematopoietic stem cells are difficult to survive in the bone marrow, and can only survive if they are irradiated with radiation or the drug is destroyed in the environment in which the bone marrow is located (bone marrow). In recent years, research reports in Japan and abroad have shown that if a large number of hematopoietic stem cells are transplanted into an individual, hematopoietic stem cells can be transplanted without destroying the bone marrow environment.

However, due to the limited number of donor-derived hematopoietic stem cells, this method of massive transplantation of hematopoietic stem cells is not feasible. The research team used this discovery of the proliferation culture system to successfully culture a small number of (50) hematopoietic stem cells to produce sufficient hematopoietic stem cells. And it does not need to destroy the bone marrow environment, it can be safely and easily carried out, which is the latest method for transplanting hematopoietic stem cells.

to sum up
The research team used mouse hematopoietic stem cells to conduct research and successfully proliferated in the long-term culture system of hematopoietic stem cells by using PVA, the main component of liquid glue. Moreover, this culture system has the possibility of being applied to human hematopoietic stem cells. The above results paved the way for a new generation of stem cell therapy for blood diseases including leukemia, and also made a great contribution to basic research in the field of stem cells. Since PVA is an inexpensive chemical used daily and can easily reach the level of pharmaceutical manufacturing, it will make a significant contribution to reducing the cost of stem cell treatment in the future.