You might have heard of bone marrow transplantation before. The public commonly uses the term “bone marrow transplantation” for “hematopoietic stem cell transplantation.” It does not transplant any bone marrow, let alone pump keel water (cerebrospinal fluid); instead, it transfers hematopoietic-related cells in bone marrow. Hematopoietic stem cells are transplanted into those who cannot produce healthy blood cells due to their illnesses.
In the early days, physicians extracted around 500-1,000 ml of bone marrow from donors (about 2-5% of the donor’s bone marrow) and separated hematopoietic stem cells from it. Extracting this bone marrow required 100-200 punctures of the donor’s iliac bone (one of the pelvic bones). Donors needed to be anesthetized and experienced discomfort after the procedure. Only loving, caring donors were willing to go through it.
Since hematopoietic stem cells usually run into peripheral blood, peripheral blood stem cell transplantation (PBSCT) became available in the late 20th century. Physicians carrying out peripheral blood stem cell transplantation use drugs or leukocyte production hormone (G-CSF) to first stimulate hematopoietic stem cells in the bone marrow. Then some of the hematopoietic stem cells will enter the peripheral blood, and then collect the cells with a machine. Finally, the physicians enable the stem cells to return to the donors’ bodies, after the peripheral blood stem cells have been frozen for a while. Because donors do not require anesthesia and experience less discomfort than with the traditional method, it has become the mainstream approach in recent years.
In Taiwan, the healthcare institution associated with peripheral blood stem cell transplantation will ask the donor to receive five injections of leukocyte-producing hormone and then take hematopoietic stem cells. Usually, the donor will take the first four injections in a nearby institution where he/she lives. The donor receives the fifth shot in the Hualien Tzu Chi Hospital, where the hospital takes the blood to test the donor’s response to leukocyte-producing hormones. If there is no response or it produces a poor result, another shot of leukocyte-producing hormone or other medicines is needed to improve the outcome. After taking an extra injection, the physician will request the donor undergo a bone marrow aspiration, if the result is still unsatisfactory.
Why do some people fail to satisfactorily respond to leukocyte-producing hormones? This question might have been lingering in the minds of many specialists. In the past, researchers found that those who did not respond well to the white blood cell production hormone appeared to be skinnier (with lower BMI). Since the donor’s blood samples are so precious, the researchers could not obtain more samples for further analysis.
The situation has improved dramatically due to the advancement of technology. Professor Der-Shan Sun of the Department of Molecular Biology and Human Genetics has worked with Dr. T.F. Wang from the Department of Hematology and Oncology at Hualien Tzu Chi Hospital for years. They collected residual blood samples from 309 donors who came to Tzu Chi Hospital to assist with hematopoietic stem cell transplants.
After separating the cells and plasma, the research team members employ the latest technology to analyze cytokines in the plasma. This new technique allows them to utilize a minimal number of samples. Researchers found that for those who did not respond well to the leukocyte production hormone, their plasma levels of interferon-Ƴ (IFN-Ƴ), interleukin-22 (IL-22), and tumor necrosis factor-ɑ (TNF-α) decreased.
In addition to having a lower BMI, why did these donors also have lower levels of the three cytokines? Professor Sun pointed out that it may be because people with higher BMI (obese people, for instance) usually have chronic inflammation, so the three inflammation-related cytokines are more elevated. But this is only a speculation, and it need be explored with further research.
What’s next? Besides collecting more samples, Professor Sun’s research team wishes to explore different approaches, hoping to find the decisive factors that affect donors to have a satisfactory response to leukocyte production hormone, to optimize hematopoietic stem cell transplantation.
Wang, T. F., Liou, Y. S., Chang, H. H., Yang, S. H., Li, C. C., Wang, J. H., & Sun, D. S. Correlation of Body Mass Index and Proinflammatory Cytokine Levels with Hematopoietic Stem Cell Mobilization. J. Clin. Med. 2022, 11, 4169. https://doi.org/10.3390/jcm11144169