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Bone marrow in a test tube

K. S. Jayaraman

doi:10.1038/nindia.2008.263 Published online 23 August 2008

Vaijayanti Kale

Indian biologists have developed a method to create an "artificial bone marrow like micro-environment" (ABME) fulfilling a long felt need of stem cell therapists.

The artificial system may eventually allow scientists generate expanded populations of blood forming stem cells in a test-tube for use in treatment of certain diseases.

Vaijayanti Kale of the National Centre for Cell Science (NCCS) in Pune and Lakshmi Charan Padhy of the Tata Institute of Fundamental Research (TIFR) have filed an International patent for their invention. They say it will not only be useful in stem cell transplantations and regenerative medicine but have industrial applications as well.

The scientists have created an environment in a test tube that mimics that of natural bone marrow. Marrow is the principal site in the human body for the formation of blood as also a host of stem and "progenitor" cells that can give rise to a wide variety of differentiated cells that constitute the human body.

The team hopes to use the ABME in pre-clinical trials with funding expected from India's Department of Biotechnology (DBT) which has shown interest following Kale's presentation of the work before an expert committee last month. Once approved, multi-centric pre-clinical trials will be initiated with the involvement of clinical centers and industrial partners, Kale told Nature India.

Since stem cells naturally occur in very small numbers in the body, it is difficult to recover them in sufficient numbers for effective use in the treatment of serious disease conditions such as aplastic anemia or malignant lymphoma, Kale explained. One way to overcome this limitation, she said, is to develop methods by which a small number of stem cells isolated from the body can be expanded (or multiplied) outside the body (in vitro) in a manner that is faithful to the natural process of expansion taking place inside the body (in vivo).

Manipulation of stem cells in vitro has not been able to achieve "desired fate" in vivo till date because "such attempts take their toll on the stem-cell specific properties," Kale said. She and her colleague Padhy overcame this problem by "priming" the in vitro system with certain biological, chemical and immunological entities, called "hematomodulators" to induce a "directed or specialized signaling" that would modulate various aspects of stem cell functions in a pre-determined manner. The duo succeeded in identifying and characterizing such entities.

By combining suitable cells from the bone marrow and a medium supplemented with hematomodulators, the team was able to create an in vitro system simulating the actual micro-environment in the bone marrow. Through four sets of experiments the researchers have shown that this artificial system — ABME — is capable of inducing and regulating the stem cells to self-renew or differentiate into specialized cells for a variety of applications in regenerative medicine.

Besides providing an environment conducive to the regulated growth and proliferation of blood cells, the ABME will be useful for evaluating bone marrow function in healthy and diseased bone marrow cells, the researchers say. It will also help minimize or eliminate 'graft versus host' disease observed in bone marrow transplantation. According to Kale, the ABME may also find use in the discovery of new drugs to regulate one or more steps in hematopoiesis — the process of formation of different blood cells — that is critical for human health.