Lecture to ASIA (American Spinal Injury Association), Denver, 14-16/05/2004

Activated Autologous Macrophages Therapy for Spinal Cord Injury: characterization of the cellular phenotype

Ina Sarel, Shahar Ish-Shalom, Ronit Bakimer, Orly Aziz, Eilat Bain, Michal Schrift-Tzadok, Marina Bubis, Yona Geffen, Jonathan B. Marder, Ziv Shulman and Eti Yoles
Proneuron Biotechnologies, Ness Ziona, Israel

Objective: Complete spinal cord injury leads to irreversible motor and sensory functional loss. The immune system is the body's machinery for wound healing and repair. However, the central nervous system's wound-healing response is less effective because of its "immune- privileged" character. Spinal cord injured rats, implanted with macrophages that were previously co-incubated with sciatic nerve or skin, show significantly improved functional recovery. Based on the encouraging preclinical animal results, we are conducting a phase II clinical trial of a cell therapy for patients with acute spinal cord injury. Here we report on characterization of the therapeutic macrophages.

Design: Monocytes isolated from peripheral blood of human donors were stimulated by co-incubation with skin tissue, producing a distinct cellular phenotype associated with wound healing.

Methods: The incubated cells were analyzed for morphological characteristics, the expression of membrane markers and cytokine secretion.

Results: Skin co-incubation caused significant increase in granule number and size, and changes in granule contents. Skin-coincubated macrophages expressed higher levels of the costimulatory molecules CD80 and CD86, and of adhesion molecule ICAM1 (CD54), reminiscent of antigen presenting cells. Additionally, co-incubation with skin resulted in increased secretion of the proinflammatory cytokine interleukin 1-beta and of Brain-Derived Neurotrophic Factor.

Conclusions: The above features of skin-coincubated macrophages suggest possible mechanisms by which they may support an immune response that promotes neuronal cell survival and repair.