Reviews: Space-time considerations for hematopoietic stem cell transplantation by Deepta Bhattacharya.

by Alexey Bersenev on August 3, 2008 · 0 comments

in niche, reviews

Have you ever asked yourself: “Why do I do this research? How can patients in the clinic benefit from my research? How can i make it important for clinic?

I did, I asked myself many times in terms of study of blood-forming system and hematopoietic stem cells (HSC). I was lucky and happy to find answers for these question in the last review – Space-time considerations for hematopoietic stem cell transplantation, which came up from the Irving Weissman group at Stanford University. So if you study hematopoietic stem cells and ever asked yourself about clinical relevance – you must read it!

Fortunately, HSC possess several unique properties that have allowed them, in the context of bone marrow transplantation, to become the only type of stem cell in routine clinical use.

Unfortunatelly many side effects and possible complications make the bone marrow transplant procedure very harmful for the patients.

Thus, the risks associated with these regimens discourage the use of HSC transplantation for the treatment of disorders that are not immediately fatal.

Here is where our research comes in to help and improve HSC transplantation procedure in clinic – make it safer and more accessible.
The main focus of the review is making more rooms available – e.i. “niche space” which could limit HSC engraftment.

The concept of the need for space for transplanted hematopoietic cells has been controversial. Early experiments by Micklem and colleagues suggested that free space or empty niches were a limiting factor to the productive engraftment of bone marrow cells into unconditioned recipients. Later studies by Brecher, Micklem and colleagues, however, concluded that space was not an important factor to donor bone marrow engraftment and that specialized sites to allow for the proliferation of donor cells likely did not exist.

Finally, the conclusion from many studies is that we need to clean niches to increase engraftment! So we really really need conditioning, and even –

reduced-intensity conditioning regimens may be insufficient to create space for transplanted HSC and that fully myeloablative regimens must be employed.

But current methods of conditioning such as irradiation and chemotherapy give a lot of side effects that make procedure risky. So, new methods should be applied, which come from “the bench”. One of the modern approaches is antibody administration against HSC surface markers, which is able to clean niches transiently long enough for engraftment of donor cells.

Another way to improve HSC procedure in clinic is to solve the problem of delayed immune reconstitution. Here transplantation of purified common myeloid or lymphoid progenitors to addition of HSC could be helpful. There are a few experimental results to support that.

Another way to improve HSC procedure in clinic is to solve the problem of delayed immune reconstitution. Here transplantation of purified common myeloid or lymphoid progenitors to addition of HSC could be helpful. There are a few experimental results to support that.

The field of bone marrow transplantation has made remarkable strides since the first clinical attempts by Thomas and colleagues. Improved methods for HLA typing and maintenance of donor registries, advancements in T cell depletion methods to minimize GVHD, new broad-spectrum antimicrobial drugs, and better conditioning regimens have brought us to a point where 50 000 bone marrow transplants are now performed annually.

Nevertheless, there is still considerable room for improvement at all stages of the process as it is currently performed. In an ideal setting, highly specific conditioning drugs, such as antibody reagents, would be used to eliminate host HSC and graft-reactive lymphocytes prior to transplantation. Transplanted progenitor cells would then mediate rapid immunity without GVHD prior to lasting donor HSC-derived multilineage reconstitution.

Idealized model for HSC transplantation. Following antibody-based ablation of host HSC and mature lymphocytes (green), transplantation of progenitor cells (blue) and HSC (red) from a donor would mediate rapid and sustained hematopoietic reconstitution. (credit: Deepta Bhattacharya & Irving Weissman, 2008.

Very good review! Easy to read. Highly recommended!

(download full text pdf)

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