1:47 PM
Nov 30, 2017
 |  BC Innovations  |  Targets & Mechanisms

All-purpose HSCs

UCSD spins out GenStem to develop HSC therapies for genetic diseases

While most eyes are on hematopoietic stem cells for their ability to treat blood cancers, a UCSD group has built a body of work showing the immune cell precursors can treat diseases with no relation to the immune system, and has spun out GenStem Therapeutics Inc. to develop the technology.

The company was formed last year based on work from the lab of Stephanie Cherqui, an associate professor in the Department of Pediatrics at the University of California San Diego. Its funding is undisclosed.

In the last month, the researchers have signed a deal with gene and cell therapy company Avrobio Inc. to co-develop a program in cystinosis, and published a preclinical study in Science Translational Medicine showing the cells can be used to treat the neurological disorder Friedreich’s ataxia.

Bone marrow transplants have long been used in oncology, sickle cell disease and a handful of other indications in which immune cells are cancerous or defective. The procedure replaces the diseased cells with hematopoietic stem cells (HSCs) from a disease-free donor that differentiate into mature cells with the relevant myeloid or lymphoid phenotypes.

Cherqui told BioCentury that although it was unclear whether or how HSCs could treat non-immune indications, the stem cells had been shown to secrete paracrine factors and vesicles carrying molecules that are “good for cells.” She tested the idea on the lysosomal storage disorder cystinosis, a multisystem disease involving kidney and eye pathology that is caused by a mutation in the lysosomal cystine transporter gene CTNS.

In a series of studies conducted between 2009 and 2016, her group showed transplantation of HSCs expressing a normal copy of CTNS successfully treated symptoms in mice. The key feature, according to Cherqui, was the mechanism her team uncovered. Instead of secreting factors, the group demonstrated the cells used a previously described cellular structure -- tunneling nanotubes -- to rescue the genetic disorder.

HSCs are destined to give rise to immune and blood cells, and therefore don’t regenerate kidney or eye tissue. Cherqui’s team showed that instead, transplanted HSCs homed to damaged tissues and differentiated into macrophages that formed nanotube passageways to the diseased cells. The macrophages then passed healthy lysosomes carrying wild-type CTNS protein from themselves through the nanotubes to treat the diseased cells (see “HSC Highways”).

Figure: HSC highways


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