Is this truth?
(Cellular Immunology, 2009) Mesenchymal Stem Cells as Anti-inflammatories: Implications for Treatment of Duchenne Muscular Dystrophy
1Thomas E. Ichim, 2Doru T. Alexandrescu, 3Fabio Solano, 3Fabian Lara, 4Rosalia De Necochea Campion, 5Eugenia Paris, 6Erik J Woods, 7Michael P Murphy, 8Constantin A Dasanu, 9Amit N Patel, 10Annette M Marleau, 1*Neil H. Riordan
1Medistem Inc, San Diego, USA; 2Georgetown Dermatology, Washington DC, USA;3Institute for Cellular Medicine, Panama City, Panama; 4University of California, San Diego, California; 5Hospital CIMA, San Jose, Costa Rica; 6General Biotechnology, Indianapolis, Indiana; 7Division of Medicine, Indiana University School of Medicine, Indiana, USA; 8Department of Hematology and Medical Oncology, St Francis Hospital and Medical Center, Hartford, CT; 9Dept of Cardiothoracic Surgery, University of Utah, Salt Lake City, Utah, USA; 10Department of Surgery, University of Nebraska Medical Centre, Omaha Nebraska
Duchenne muscular dystrophy (DMD) is a lethal X-linked musculodegenerative condition consisting of an underlying genetic defect whose manifestation is augmented by inflammatory mechanisms. Previous treatment approaches using gene replacement, exon-skipping or allogeneic cell therapy have been relatively unsuccessful. The only intervention to mediate improvement in survival, albeit minor, is glucocorticoid treatment. Given this modality appears to function via suppression of underlying inflammation; we focus this review on the inflammatory response as a target for mesenchymal stem cell (MSC) therapy. In contrast to other cell based therapies attempted in DMD, MSC have the advantages of: a) ability to fuse with and genetically complement dystrophic muscle; b) possess anti-inflammatory activities; and c) produce trophic factors that may augment activity of endogenous repair cells. We conclude by describing one practical scenario of stem cell therapy for DMD.
...."Case Report of Stem Cell Therapy for DMD
We report a case study of a 23 year old male diagnosed with DMD at age 3, who manifested a progressive decrease in muscular strength and became wheelchair bound at age of 12. Supportive treatment with intermittent courses of prednisone, pain management, along with physical therapy was provided. Frequent respiratory infections secondary to a poor respiratory effort with decrease clearance of the secretions were managed with standard antibiotic therapy. On August 5-14th, 2008, the patient was treated with a combination of ERC and CD34 umbilical cord blood, mixed lymphocyte reaction-matched positive cells,subsequently on November 25-28, the patient received another course of therapy including placental matrix derived mesenchymal stem cells (Table 1). Cells were prepared and administered as previously described by us [148, 149]. No adverse events were associated with the stem cell infusion. A significant increase in muscle strength occurred in all the muscle groups, and was accompanied by an increase in the functional capacity of the patient. Thus, a pre-transplantation strength of 2-2.5/5 in the neck, shoulder, upper, and lower extremities began to improve after each of the two stem cell administrations, and reached a final 4/5 level 1 month after second transplantation treatment. The increments in muscle strength after the two stem cell administration appeared to be additive, with most benefit recorded after the second. Upper extremity improvement in strength evolved from the incapacity to lift against
gravity before the transplantation towards the ability to lift 2 lbs weights after the procedure. Trunk balance and strength were also markedly improved. The patient gained 20 lbs, along with an increased general activity level. The frequency of respiratory infections decreased from 3-4/year before stem cell therapy to none. The inspiratory effort improved from -32 to -40 cm H20. A muscle biopsy taken in January 2009 demonstrated normal (>50%, normal = 50-100% expression of normal-molecular size) levels of muscular dystrophin. The improvement in muscular strength, clinical respiratory function, and general level of activity are maintained to date.
To our knowledge this is the first report of profound dystrophin expression occurring in a non-ambulatory DMD patient after ERC treatment .......