MaxGel Developed by Dr. Hall

Stem cells can express therapeutic genes for cancer therapy. The ability of MaxGel to increase cell proliferation and tumor formation and improve subsequent delivery of therapeutic stem cells for the treatment of prostate cancer was studied.

In order to influence tumor formation, xenografts were induced in nude mice by subcutaneous inoculation of PC3 human bone metastatic prostate cancer cells with and without MaxGel. Mesenchymal stem cells were engineered with the yeast cytosine deaminase gene that converts non-toxic 5-fluorocytosine into the highly toxic anti-tumor 5-fluorouracil, which selectively targets tumor cells. This engineered stem cell line (CD-MSC) was delivered into nude mice after tumor formation with and without MaxGel to determine the degree of tumor regression.

After 14 days, MaxGel (1 mg/ml) caused significantly larger tumors in mice than did PC3 tumor cells alone. Following delivery of 2 x 106 CD-MSC delivered intravenously into nude mice (n=9 each group) either alone or in conjunction with MaxGel, it was determined that MaxGel was able to cause a significant reduction of tumor size due to its ability to augment delivery of CD-MSC to the tumor site and facilitate tumor killing by the therapeutic stem cells.

Developed by Dr. Hall, MaxGel promoted significantly greater proliferation of tumor cells in a xenograft tumor model in nude mice. Even in the presence of this increased tumor mass, MaxGel provided a superior support matrix for therapeutic stem cell growth and differentiation, resulting in greater tumor necrosis than using therapeutic stem cells alone.

Laminin-111 Developed by Dr. Hall

Laminin-111 is a structural molecule that can be systemically delivered to skeletal and cardiac muscles. Laminin-111 restores lost cellular adhesion found in several forms of muscular dystrophy through enhancement of a laminin receptor expressed in all muscular dystrophy patients.

A single systemic dose of LAM-111 delivered through IV to the mdx mouse model of DMD distributed to all cardiac and skeletal muscles resulting in a profound decrease in muscle disease. Multiple systemic doses of LAM-111 delivered through IV to the dyW mouse model of MDC1A distributed to all skeletal muscles and extends life, improves mobility and also resulted in a profound decrease in muscle disease

Dr. Hall has developed the only known method in the world to produce human LAM-111 and other extracellular matrix proteins in cell culture. DMD clinical trials are planned within the next 2 years.

Treatment of Traumatic Brain Injury

It is estimated that more than 2.5 million Americans live with the devastating consequences of a traumatic brain injury (TBI).

Acute treatment of TBI is limited to controlling intracranial pressure and optimizing cerebral perfusion pressure to prevent further intracranial damage, while chronic treatment centers on motor, cognitive, and behavioral rehabilitation. No current therapy alters the underlying pathologic processes via cellular salvage, repair, or replacement.

In a rat model of TBI in Dr. Hall's lab, neural stem cells (NSC) were transplanted into the injured brain to determine if the NSC migrated to the site of injury and fully restored motor function.

It was shown that intracerebral rat neural stem cell placement 7 days after moderate TBI improves motor function and slightly improves cognitive function recovery.

The placement and method of delivery are important factors in cell survival and may improve cell survival and cognitive recovery. Using biomaterials-based delivery is one method that could improve efficacy.