Autologous stromal vascular fraction cells: A tool for facilitating tolerance in rheumatic disease
Cellular Immunology Journal Homepage: www.elsevier.com/locate/ycimm
Cellular Immunology 264 (2010) 7–17
Thomas E. Ichim a,*, Robert J. Harman b , Wei-Ping Min c , Boris Minev d,e, Fabio Solano f , Jorge Paz Rodriguez g , Doru T. Alexandrescu h , Rosalia De Necochea-Campion d , Xiang Hu i , Annette M. Marleau j , Neil H. Riordan a
Since the days of Medawar, the goal of therapeutic tolerogenesis has been a ‘‘Holy Grail” for immunologists. While knowledge of cellular and molecular mechanisms of this process has been increasing at an exponential rate, clinical progress has been minimal. To provide a mechanistic background of tolerogenesis, we overview common processes in the naturally occurring examples of: pregnancy, cancer, oral tolerance and anterior chamber associated immune deviation. The case is made that an easily accessible byproduct of plastic surgery, the adipose stromal vascular fraction, contains elements directly capable of promoting tolerogenesis such as T regulatory cells and inhibitory macrophages. The high content of mesenchymal and hematopoietic stem cells from this source provides the possibility of trophic/regenerative potential, which would augment tolerogenic processes by decreasing ongoing inflammation. We discuss the application of this autologous cell source in the context of rheumatoid arthritis, concluding with some practical examples of its applications.
In conclusion, we propose that SVF cells represent a novel, easy to implement cell therapy that warrants investigation as a monotherapy or adjuvant to tolerance induction protocols. The fact that autotransplantation of adipose tissue is part of standard cosmetic surgery practice without adverse events [227,228], as well as our pilot clinical data with SVF in multiple sclerosis , and RA, supports the notion of feasibility. Of the components of SVF, the MSC fraction may provide direct immune regulatory activities, as well as stimulation of tissue regeneration, thus decreasing ‘‘danger signals” which inhibit tolerogenesis. CD34 cells found in SVF have the potential to immune regulate, although further work in this area is necessary. The recent finding of enhanced Treg numbers and activity in adipose tissue suggests SVF may be a previously unrecognized source of regulatory cells capable of in vivo expansion subsequent to administration . In a previous study we reported treatment of three patients with multiple sclerosis with autologous SVF, which underwent a profound clinical response . The cases presented here serve to expand on the ‘‘clinical signal” that an anti-inflammatory/disease modifying effect may be achieved using the simple process of autologous SVF administration. While future studies are obviously needed to confirm these preliminary observations, the establishment of feasibility and administration protocols serves as a basis for future studies. An interesting question presented by these studies is whether the adipose resident Treg cells may also have deregulated function as found in the periphery of patients with RA . This is currently being investigated.