The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Stem Cell Breakthrough: Direct Conversion of Human Skin to Blood

A breakthrough in Canadian stem cell research this week, published in Nature, as researchers led by Dr. Mick Bhatia of the Stem Cell and Cancer Research Institute at McMaster University have devised methods to differentiate human skin cells into blood cells. In many differentiation protocols researchers are forced to first reprogram cells to a pluripotent intermediate before differentiating these primitive cells into the desired cell type. The protocol developed by Dr. Bhatia utilizes a ‘trans-differentiation’ process where skin cells are turned directly into blood cells without the need for reprogramming to a primordial state. As a result, the differentiation process is not only simpler, but safer from a therapeutic standpoint.

In order to produce blood progenitors researchers activated hematopoietic transcription through ectopic expression of the stem cell gene OCT4 in conjunction with a specific cytokine treatment. This stimulated the formation of multipotent CD45-expressing blood progenitor cells that could give rise to multiple lineages of blood cells including white blood cells, red blood cells, and platelets. Differentiation protocols requiring the generation of pluripotent intermediates introduce safety concerns as residual pluripotent cells remaining after the differentiation process can form tumours following transplantation in humans. These tumours, also known as teratomas, result from the spontaneous differentiation of pluripotent cells in the body. By taking a direct approach Dr. Bhatia’s team has circumvented this risk and created a protocol to produce safe and clinically relevant populations of blood cells.

Another beauty of this protocol is that it represents an autologous (self) source of therapeutic cells. Patients could potentially have small grafts of their own skin removed, cultured in vitro, and then trans-differentiated into blood cells of their own genetic make-up. These cells could then be used for blood transfusion without the concern of immune rejection. The barrier that remains is finding ways to scale these blood cells up following differentiation to produce quantities of cells that would be useful for transfusion. Once this is complete, the protocol can be taken to the clinic and tested in humans.

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