On May 12th, the New England Journal of Medicine published a paper on “the Clinical Implications of Basic Research of Blood and Bone”. The paper gave an overview of hemopoietic stem cells (HSCs), from pioneering research dating back to the 1950’s, to the recent challenges and research developments. David TScadden, MD, authored the paper and analyzed the limitations of incorporating HSC transplant into a routine clinical practice as well as the advancements in the field of stem cell therapy. The research has made use of fluorescently engineered Hoxb5gene to find out regions in the marrow bone,which are rich in long-term hemopoietic stem cells. The finding has traced the regulatory niche of HSCs and the association between the HSCs, the blood vessels, and the endothelial cells.
Over the past six decades, hemopoietic stem cells have been widely researched upon, as scientists delve into understanding the mechanism that governs the replenishing ability of stem cells. Hemopoietic stem cells are the stem cells that are developed by progenitor cells, known as mesodermal hemangioblast cells. All blood cells from lymphoid and myeloid lineages are proliferated from HSCs since the HSCs are responsible for generating blood and immune cells. The HSCs have the ability to isolate themselves from other cells in the bone marrow; they leave the marrow and flow into the bloodstream to differentiate into the blood cells that need to be replenished. When their job is done, they are excreted out of the circulatory system by apoptosis (programmed cell death).
Research has shown that HSCs are found in adult bone marrow, peripheral blood and umbilical cord blood and their multipotent, self-renewing abilities have led the researchers to closely study HSCs and make use of them in the treatment of life-threatening blood diseases. Research has shown that hemopoietic stem cells can be categorized into two types:short term and long term. The long-term HSCs are the prime focus of HSC therapies due to their longevity in the system and renewal ability.
Laboratory and clinical experimentations into the use of HSCs and HSC transplantation for lethal blood diseases can be dated back to the 1950’s. Despite the potential of this groundbreaking research to be incorporated into clinical use, there have been many roadblocks on the way. The initial complications consisted of an immunologic matching problem between the donor and recipient of HSCs, graft versus host diseases and genotoxic conditioning. To find solutions to the problems that failed HSCs transplantation in the initial years after its discovery, Irvine Weissman and team pioneered the research of using antibodies to sub fractionate bone marrow cells and analyze their regenerative capacity in HSC transplantation.
This pioneering research was taken forward by Chen et al, who have identified a gene named Hoxb5 gene in the long-term HSCs. The team has engineered the Hoxb5 gene with another fluorescent gene in mice. These fluorescent genes are manipulated in such a manner that their expression is manifested by giving out illumination in the regions of bone marrow that contain long-term HSCs. Visualizing long-term HSCs will help the scientists stride forward in knowing the regions rich in HSCs.
Light-based cell sorting and microscopic imaging facilitated Chen and team to find out the close proximity of HSCs to blood vessels and endothelial cells. Flushing of bone marrow from long bones has helped them limit their analysis of central regions of the bone marrow where HSCs are concentrated. Based on previous clinical transplantations, it has been observed that blood vessel integrity is temporarily compromised and endothelial cells are dysfunctional. Complementing this finding,Chen and team made a convincing case which suggested that the HSCs are mixed with endothelial cells and these cells work as a regulatory factor for the proliferation of HSCs.
Visualizing HSCs and isolating them from other cell types in the marrow bone can help find answers to many mind-boggling questions that have limited the clinical use of stem cell therapy for severe blood diseases and cancers. Now that scientists have pinpointed the areas where HSCs are in abundance, clinicians can isolate the stems cells that are highly potent. This will also help them differentiate HSCs from low potency or abnormal cells that may be another cause for a failed stem cell therapy. Using high potent HSCs will assist them to get improved results of stem cell therapy, where the diseased cells are replenished with healthy cells with improved efficacy. This may also serve as a milestone for regenerative medicine. Once the scientists find out the complex mechanisms of the formation and differentiation of a stem cell into different cells and tissues along with the contributing elements and growth factors, studies can be done to find insights into tissue regeneration.