Recently some folks and I were fascinated by a concept based on developing cell capturing and cell trafficking control implantable devices. The concept is based on known receptor-ligand interactions between circulating bone marrow cells or seeded cells and defined factors embedded in the device. This approach may provide a new generation of cell therapies in the future.
Lately, some of these devices entered the commercialization phase and were licensed by companies. I’d like to give you a brief overview of some of these kind of devices.
1. “Jianyi Zhang‘s patch”
device-patch: PEGylated fibrinogen, bound with recombinant SDF-1
how it works: Patch implanted in myocardium released SDF-1 – homing factor for hematopoietic (Sca1+/cKit+) cells. Recruited bone marrow progenitor/stem cells to mediate heart muscle and regeneration.
IP: US patent application # 20050118144
potential application: heart muscle regeneration
publications: Zhang G, et al. Controlled release of stromal cell derived. Factor-1α in situ increases stem cell homing to the infarcted heart. Tissue Eng. 2007;13(8):2063-2071
2. “Michael King‘s device”
device: P-selectin–coated microtubes implanted as arteriovenous shunt
how it works: P-selectin triggers mobilization of hematopoietic stem/progenitor cells from bone marrow. Enriched stem cell fraction could be collected and eventually expanded and/or transplanted.
separation of cancer cells – TRAIL-coated device:
…device that filters the blood for cancer and stem cells. When he captures cancer cells, he kills them. When he captures stem cells, he harvests them for later use in tissue engineering, bone marrow transplants…
IP: Michael King’s (U of Rochester) US patents: 20060183223, 20070178084;
Jeffery Karp (MIT), technology exclusively licensed by CellTraffix
potential application: hematology, oncology
publications: Wojciechowski JC, et al. Capture and enrichment of CD34-positive haematopoietic stem and progenitor cells from blood circulation using P-selectin in an implantable device. Br J Haematol. 2008 March; 140(6): 673–681 (OA)
Finally, most intelligent device from new generation:
3. “David Mooney‘s device”
devices in work: In situ bioreactive devices (iBD). Examples:
- PLG matrix with mobilized GM-CSF and tumor antigen. G-CSF attracts dendritic cells, which start to expand and present tumor antigen. After release, antigen-presenting dendritic cells migrate to lymphoid organs and activate specific anti-tumor clon of cytotoxic T-cells.
- Alginate scaffold with VEGF and endothelial progenitors. VEGF could attract endogenous endothelial cells or support scaffold-embed ones and stimulate local neovascularization.
IP: David Mooney’s lab at Harvard University US patents; technology licensed by InCytu
potential application: immunotherapy in oncology, tissue regeneration and therapuetic angiogenesis
publications: Ali OA,et al. Infection-mimicking materials to program dendritic cells in situ. Nat Mater. 2009 Feb;8(2):151-8
Silva EA, et al. Material-based deployment enhances efficacy of endothelial progenitor cells. PNAS 2008 Sep 23;105(38):14347-52 (OA)
So, ideally device should be composed of biodegradable material with some mobilized factors and dedicated to recruit desired cell population, modify their qualities and controllably release them for in situ therapy. Development of those devices demonstrates a good example of a multidisciplinary approach, coming from tissue engineering principals. Future development of such devices can provide an absolutely new way of cell-based therapies.