Lecture to APS (American Paraplegia Society) – 7-9/09/2004 in Las Vegas, Nevada

Characterization of PROCORD – macrophage cell therapy for Spinal Cord Injury

Marina Bubis, Ina Sarel, Shahar Ish-Shalom, Orly Aziz, Eilat Bain, Michal Schrift-Zadok, Jonathan B. Marder, Ronit Bakimer, Yona Geffen, Ziv Shulman, Eti Yoles

Background: The aim of this study was to characterize ProCord, an experimental cell therapy for spinal cord injury (SCI). Procord consists of autologous macrophages that have been incubated with skin. Macrophages and other immune cells participate in normal wound healing in most tissues, but their activity in the damaged central nervous system is repressed by “immune privilege”. Injection of the skin-coincubated macrophages into the damaged spinal cord is designed to overcome the hostile tissue environment, thereby promoting neuronal survival and regrowth. In animal models, the therapy led to improved functional recovery. Phase II clinical trials are now underway. Phase I results are presented in a separate abstract.

Design: A laboratory study was performed using blood-derived monocytes from SCI patients and healthy donors, activated by incubation with autologous or heterologous skin respectively.

Methods: Monocytes were isolated from peripheral blood and incubated with or without skin tissue. The resultant macrophages were then analyzed for morphological characteristics, cell membrane markers expression and cytokine secretion.

Results: Incubation of the cells with skin tissue promoted the accumulation of refractive, intracellular granules. In cells incubated without skin, the granules were fewer and smaller. Also, specific probes indicated different granule compositions. Skin co-incubated macrophages expressed high levels of the molecules participating in cell-cell interaction (ICAM-1) and antigen presentation (CD80, CD86). Incubation with skin affected the secretion of cytokines (increased Interleukin 1β and Interleukin 6), neurotrophic growth factors (increased BDNF, no secretion of NT3 or NT4/5) and chemokines (increase in Interleukin 8).

Conclusions: Recent findings on protective autoimmunity and cytokine-promoted neurite outgrowth suggest possible mechanisms by which Procord may aid recovery from SCI. The results presented suggest that co-incubation with skin tissue causes the macrophages to adopt a specific phenotype, with activities that may be central to the controlled immune response that supports neuronal cell survival and repair.