CD34(+) Stem Cell Therapy in Non-Ischemic Dilated Cardiomyopathy Patients.
1] Advanced Heart Failure and Transplantation Center, UMC Ljubljana, Slovenia  Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. Clinical Pharmacology & Therapeutics
(Impact Factor: 7.9).
07/2013; 94(4). DOI: 10.1038/clpt.2013.134
Recent trends indicate that patients with non-ischemic dilated cardiomyopathy represent the largest subpopulation of heart failure patients with a significant need for alternative treatment modalities. Similar to ischemic cardiomyopathy, patients with non-ischemic dilated cardiomyopathy have been found to have myocardial regions with flow abnormalities, which may represent the targets for neoagiogenetic therapies. CD34(+) stem cells might contribute to the formation of new blood vessels from existing vascular structures in ischemic tissues by the direct incorporation of injected cells into the newly developing vasculature or the production and secretion of angiogenic cytokines. The review summarizes the long-term clinical effects and potential underlying mechanisms of CD34(+) cell therapy in patients with non-ischemic dilated cardiomyopathy.Clinical Pharmacology & Therapeutics (2013); accepted article preview online 31 July 2013. doi:10.1038/clpt.2013.134.
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ABSTRACT: Heart failure (HF) is the most common cause of cardiovascular hospitalization, especially among the elderly. It has a higher mortality and morbidity than several cancers and consumes a significant portion of the health-care budget. HF with preserved ejection fraction (HFpEF) is commoner among women who may have underlying hypertension. Significant progress has been achieved in the development of lifesaving drugs for HF with reduced ejection fraction (HFrEF). However, treatment of HFpEF still poses significant challenges.
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ABSTRACT: Purpose: Because human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions. Methods: This prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or non-exudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice-conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics-OCT were performed during the six-month follow-up. Results: A mean of 3.4 million (range 1 to 7 million) CD34+ cells were isolated and injected per eye. The therapy was well-tolerated with no intraocular inflammation or hyper-proliferation. Best-corrected visual acuity and full-field ERG showed no worsening after six months. Clinical examination also showed no worsening during follow-up except among AMD subjects where mild progression of geographic atrophy was noted in both the study eye and contralateral eye at six-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in-vivo imaging using adaptive optics-OCT showed changes suggestive of new cellular incorporation into the macula of hereditary macular degeneration study eye. Conclusions: Intravitreal autologous BM CD34+ cell therapy appears feasible and well-tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration.
Copyright © 2014 by Association for Research in Vision and Ophthalmology.
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