Aekkachai Tuekprakhon1, Siripakorn Sangkitporn2, Adisak Trinavarat1, Aulia Rahmi Pawestri3, Visit Vamvanij4, Monchai Ruangchainikom4, Panya Luksanapruksa4, Phitchapa Pongpaksupasin1,5, Areerat Khorchai2, Acharaporn Dambua2, Patcharaporn Boonchu2, Chonlada Yodtup2, Mongkol Uiprasertkul6, Somchai Sangkitporn7, La-Ongsri Atchaneeyasakul8. 1. Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok Noi, Bangkok, 10700, Thailand. 2. Stem cell and Regenerative Medicine Center, Department of Medical Sciences, Ministry of Public Health, National Institute of Health, 88/7 Tivanon Road, Muang, Nonthaburi, 11000, Thailand. 3. Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia. 4. Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 5. Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 6. Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 7. Stem cell and Regenerative Medicine Center, Department of Medical Sciences, Ministry of Public Health, National Institute of Health, 88/7 Tivanon Road, Muang, Nonthaburi, 11000, Thailand. somchai.s@dmsc.mail.go.th. 8. Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok Noi, Bangkok, 10700, Thailand. atchanee@hotmail.com.
Abstract
BACKGROUND: Retinitis pigmentosa (RP) is a progressive inherited retinal disease with great interest for finding effective treatment modalities. Stem cell-based therapy is one of the promising candidates. We aimed to investigate the safety, feasibility, and short-term efficacy of intravitreal injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in participants with advanced stage RP. METHODS: This non-randomized phase I clinical trial enrolled 14 participants, categorized into three groups based on a single dose intravitreal BM-MSC injection of 1 × 106, 5 × 106, or 1 × 107 cells. We evaluated signs of inflammation and other adverse events (AEs). We also assessed the best corrected visual acuity (BCVA), visual field (VF), central subfield thickness (CST), and subjective experiences. RESULTS: During the 12-month period, we noticed several mild and transient AEs. Interestingly, we found statistically significant improvements in the BCVA compared to baseline, although they returned to the baseline at 12 months. The VF and CST were stable, indicating no remarkable disease progression. We followed 12 participants beyond the study period, ranging from 1.5 to 7 years, and observed one severe but manageable AE at year 3. CONCLUSION: Intravitreal injection of BM-MSCs appears to be safe and potentially effective. All adverse events during the 12-month period required observation without any intervention. For the long-term follow-up, only one participant needed surgical treatment for a serious adverse event and the vision was restored. An enrollment of larger number of participants with less advanced RP and long-term follow-up is required to evaluate the safety and efficacy of this intervention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01531348 . Registered on February 10, 2012.
BACKGROUND: Retinitis pigmentosa (RP) is a progressive inherited retinal disease with great interest for finding effective treatment modalities. Stem cell-based therapy is one of the promising candidates. We aimed to investigate the safety, feasibility, and short-term efficacy of intravitreal injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in participants with advanced stage RP. METHODS: This non-randomized phase I clinical trial enrolled 14 participants, categorized into three groups based on a single dose intravitreal BM-MSC injection of 1 × 106, 5 × 106, or 1 × 107 cells. We evaluated signs of inflammation and other adverse events (AEs). We also assessed the best corrected visual acuity (BCVA), visual field (VF), central subfield thickness (CST), and subjective experiences. RESULTS: During the 12-month period, we noticed several mild and transient AEs. Interestingly, we found statistically significant improvements in the BCVA compared to baseline, although they returned to the baseline at 12 months. The VF and CST were stable, indicating no remarkable disease progression. We followed 12 participants beyond the study period, ranging from 1.5 to 7 years, and observed one severe but manageable AE at year 3. CONCLUSION: Intravitreal injection of BM-MSCs appears to be safe and potentially effective. All adverse events during the 12-month period required observation without any intervention. For the long-term follow-up, only one participant needed surgical treatment for a serious adverse event and the vision was restored. An enrollment of larger number of participants with less advanced RP and long-term follow-up is required to evaluate the safety and efficacy of this intervention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01531348 . Registered on February 10, 2012.
Authors: Steven D Schwartz; Jean-Pierre Hubschman; Gad Heilwell; Valentina Franco-Cardenas; Carolyn K Pan; Rosaleen M Ostrick; Edmund Mickunas; Roger Gay; Irina Klimanskaya; Robert Lanza Journal: Lancet Date: 2012-01-24 Impact factor: 79.321
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