Steinberg Lab Research: Translational Research

Our overarching goal for the translational stem cell research program is to provide stroke patients with a means to recovery. With funding from the California Institute for Regenerative Medicine (CIRM) Disease Team program, the Steinberg lab and colleagues from several California institutions are developing a stem cell product that will make stem cell therapy for stroke a medical reality.

The cell line NR1, derived from the embryonic stem cell line H9 (see figure), is effective for functional recovery in multiple rodent stroke models. Other properties of the NR1 cells, such as being euploid and amenable to large-scale production, make them an excellent candidate for translation to the clinic. NR1 is the only allogeneic, non-genetically modified human neural stem cell intended for chronic stroke treatment.

Productive interactions with the Food and Drug Administration (FDA) have guided our efforts to create a stem cell product that will be safe and effective as treatment for post-stroke sequelae. Pharmacology and toxicology testing, along with further assay development, are currently underway with the goal of formalizing our Investigational New Drug (IND) application soon.

Through a multidisciplinary effort, our team is meeting the challenges of translating our basic research on stem cells for post-stroke recovery to a safe and revolutionary treatment for patients.

Dispersion, engraftment and differentiation of the hNSCs in stroke-lesioned more(A) Schematic drawing of a frontal section through the striatum illustrating the dispersion of grafted hNSCs in the focal ischemia-lesioned parenchyma (shaded area). (B, C) Photos show frontal sections through the graft in the striatum immunostained with the human specific antibodies: anti-hNuc (green in B & C) and anti-GluT1 (red, B & C) showing blood vessels and dispersed hNSCs in the graft zone. C: higher magnification of the inset in B. (D–I) Photos taken from frontal sections through the graft in the striatum double immunoprocessed for cell proliferation and neural lineage markers. (D) Note the endogenous Ki67+ cells (red cells, arrow) in the stroke damaged area and the hNuc+ (green)/Ki67- grafted hNSCs (arrowheads). (E) Examples of grafted NR1 hNSCs showing co-expression of hNuc (green) and nestin (red). (F) Confocal 3D reconstructed orthogonal images of the hNuc+(green)/DCX+(red) NSCs (arrowheads) viewed in the x-z plan on the top and y-z plan on the right. (G) Examples show the majority of grafted NSC progeny co-expressing hNuc (red) and the neuronal marker TuJ1 (green). Grafted NSCs rarely differentiate into GFAP+ astrocytes (H). In I, rare example of grafted NSC progeny becoming an oligodendrocyte identified by the expression of CNPase (green). Grafted NSCs expressed the GABAergic marker GAD65/67 (J) and rarely expressed glutamate (K). (Abbreviations: Cx: cortex, Str: striatum). Bars: (B, C) 100 µm; (D, F) 20 µm; (E, G–K) 10 µm.