Non-expanded adipose Stromal vascular fraction cell therapy for Multiple sclerosis（2）
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Second patient: A 32-year-old man was diagnosed in 2001 with relapsing-remitting MS, presenting with fatigue and depression, uneven walk pattern, cognitive dysfunction, and a progressive decline in his memory without any specific neurological symptoms. In 2002 he was started on weekly intramuscular Avonex (IFN-b1a, Biogen Idec) and has had no further exacerbations and no evidence of progressive deterioration. Patient's fatigue was treated well with Provigil, and his mood improved significantly due to treatment with Wellbutrin SR. In 2007, the patient complained of some mood changes, with more agitation, irritability, mood destabilization, and cognitive slowing. As depression was suspected in playing a central role in patient's condition, Razadyne was added to the antidepressant regimen.
In 2008, the patient was treated with two I.V. infusions of 25 million autologous adipose-derived SVF cells and multiple intrathecal and intravenous infusions of allogeneic CD34+ and MSC cells. MSC were third party unmatched and CD34 were matched by mixed lymphocyte reaction. All infusions were performed within a 10-day period and were very well tolerated without any significant side effects. The treatment plan also included physical therapy sessions.
Three months after the stem cell infusions the patient reported a significant improvement of his balance and coordination as well as an improved energy level and mood. New MRI images, obtained 7 months after the stem cell treatment showed lesions, very similar to the lesions observed before the stem cell treatment (Figure 2). Currently, he is not taking any antidepressants and is reporting a significantly improved overall condition. His current treatment regiment includes a weekly injection of Avonex, vitamins, minerals and Omega 3.
Figure 2. MRI Images obtained before (Panels A and B), and seven months after (Panel C) the stem cell treatment of patient 2. Panels A and B: Consecutive axial FLuid-Attenuated Inversion Recovery (FLAIR) images through the lateral ventricles show multiple small patches of bright signal in the periventricular and subcortical white matter, consistent with plaques of multiple sclerosis. Panel C: Axial FLAIR image shows no significant change in the multiple periventricular and subcortical white-matter plaques. (For the comparison, note that this slice is positioned similar to slice A but at slightly different scanning-angle, so it includes lesions of both slices A and B.).
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The patient was diagnosed with relapsing-remitting MS in 1993, presenting symptoms were noticeable tingling and burning sensation in the right leg, followed by paraplegia lasting almost three weeks. Neurological investigations at the time uncovered MRI findings suggestive for a demyelinating syndrome. In June of 2008, the patient was treated with two I.V. infusions of 75 million autologous adipose-derived SVF cells and multiple intrathecal and intravenous infusions of allogeneic CD34+ and MSC cells. MSC were third party unmatched and CD34 were matched by mixed lymphocyte reaction. All infusions were performed within a 10-day period and were very well tolerated without any significant side effects. His gait, balance and coordination improved dramatically oven a period of several weeks. His condition continued to improve over the next few months and he is currently reporting a still continuing improvement and ability to jog, run and bike for extended periods of time daily.
Conclusion
The patients treated were part of a compassionate-use evaluation of stem cell therapeutic protocols in a physician-initiated manner. Previous experiences in MS patients using allogeneic CD34+ cord blood cells together with MSC did not routinely result in substantial improvements observed in the three cases described above. While obviously no conclusions in terms of therapeutic efficacy can be drawn from the above reports, we believe that further clinical evaluation of autologous SVF cells is warranted in autoimmune conditions.
Competing interests
Thomas E Ichim and Neil H Riordan are management and shareholders of Medistem Inc, a company that has filed intellectual property on the use of adipose stromal vascular fraction cells for immune modulation.
Authors' contributions
All authors read and approved the final manuscript. NHR, TEI, WPM, HW, FS, FL, MA, JPR, RJH, ANP, MPM, RRL and BM conceived experiments, interpreted data, and wrote the manuscript.
Acknowledgements
We thank Victoria Dardov, Rosalia De Necochea Campion, Florica Batu, and Boris Markosian for stimulating discussions.
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