Authors' objectives: To assess the effectiveness, safety and cost-effectiveness of mesenchymal stem cells (MSC) for the treatment of retinitis pigmentosa (RP) and other degenerative retina disease (Best disease, Beatti’s macular dystrophy, cone-rod dystrophy and age-related macular degeneration).

Authors' results and conclusions: Based on the above review, there was limited fair level of evidences on MSC to be used in the management of patients with degenerative retinal disease (retinitis pigmentosa). Administration of MSC showed short term beneficial effect on vision function namely best corrected visual acuity, visual field, electroretinography recordings (for parameters: ERG amplitudes, implicit time) and vision related quality of life, during six months and up to one year, compared to baseline, as well as improve retina structural changes in the treated eye of patients with RP. Significant improvement in BCVA and VF were observed in the treated eyes. Significant improvement in the vision related QOL of patients observed at three months after BMDSC. Most participants experienced improvements in the QOL during the 12-month period after the BM-MSC injection however no significant difference from baseline by one year. Also improvement in the retina structure. The only USFDA-approved stem cell products was hematopoietic progenitor cells, derived from umbilical cord blood meant for use in patients with hematopoietic system disorders. MSC appeared safe with no ocular, systemic adverse events or hyperproliferation following MSCs injection among the study population at one year. Transient vision loss, recovered slight VF deterioration and epiretinal membrane have been reported. MSCs has a lower risk of differentiating into undesired tissues, teratoma formation, immune rejection (even from allogeneic sources), and ethical concerns to its use, compared to Retinal Progenitor Cells (RPC), Embryonic Stem Cells (ESC), and induced Pluripotent Cells (iPSC). There was no evidence retrieved on cost-effectiveness of MSC for RP and other degenerative retina disease. In Malaysia, the complete breakdown of cost of activities entailed in the testing, harvesting, isolation and storage of MSC was not able to be retrieved fully. It was said that a treatment of MSC may cost MYR60,000 to MYR80,000 consisting of 100 million cells. It was reported two patients with retinitis pigmentosa have received retinal MSC injection in Malaysia and paid MYR20,000 to MYR30,000 per procedure. The average number of discharges of patients with retinal disease (degeneration of macula and posterior pole, peripheral retinal degeneration, hereditary retinal dystrophy) in the past five years (2017-2021) was 131 discharges per year. Hence, the cost implication will be approximately MYR7,860,000 to MYR10,480,000 per year. The International Society for Cellular Therapy highlighted minimal criteria before a cell can be considered as MSC; specific immunophenotype, tissue culture plastic-adherent and multilineage differentiation. MSCs production for clinical intervention needs to comply with good manufacturing practice (GMP). Processes involved need to be defined; the source for isolation, culture methods, procedures, materials and methods used for cell culture, and quality controls. Laboratories using clinical-grade MSCs should follow regulatory agency requirements on use of equipment, reagents and supplies, established procedures, and strict safety measures. In the US, the GMP hMSC production is regulated by FDA CFR Title 21 focusing on current good tissue practice requirements. In the European Union, the GMP production is regulated under the European Regulation No. 1394/2007. The MSC collection, processing, storage and infusion shall follow the requirements of the standards, in line with the Malaysia National Organ, Tissue and Cell Transplantation Policy.

Authors' recommendations: Based on the above review, MSC has the potential to be used as a treatment modality in patients with RP & degenerative retinal disorders. However, long term effectiveness of this cell therapy including patients’ quality of life merits further research. The patient selection preferably would be those with potential for visual recovery.

Authors' methods: Studies were identified by searching electronic databases. The following databases were searched through the Ovid interface: MEDLINE(R) In-process and other Non-Indexed Citations and Ovid MEDLINE(R) 1946 to present. EBM Reviews-Cochrane Database of Systematic Reviews (2005 to March 2022), EBM Reviews-Cochrane Central Register of Controlled Trials (March 2022), EBM Reviews – Database of Abstracts of Review of Effects (1st Quarter 2022), EBM Reviews-Health Technology Assessment 1st Quarter 2022), EBM Reviews-NHS Economic Evaluation Database (1st Quarter 2022). Parallel searches were run in PubMed. Appendix 3 showed the detailed search strategies. No limits were applied to the search. The last search was run on 30 April 2022. Additional articles were identified from reviewing the references of retrieved articles. Among the tools used to assess the risk of bias and methodological quality of the articles retrieved is the Cochrane risk of bias tool and ROBINS-I. All full text articles were then graded based on guidelines from the US/Canadian Preventive Services Task Force.

Authors' identified further research: None

Project Status: Completed

Year Published: 2022

URL for published report: https://www.moh.gov.my/index.php/database_stores/store_view_page/30/394

Requestor: Ministry of Health, decision-making committee

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Malaysia

Organisation Name: Malaysian Health Technology Assessment

Contact Address: Malaysian Health Technology Assessment Section, Ministry of Health Malaysia, Federal Government Administrative Centre, Level 4, Block E1, Parcel E, 62590 Putrajaya Malaysia Tel: +603 8883 1229

Contact Name: htamalaysia@moh.gov.my

Contact Email: htamalaysia@moh.gov.my

Copyright: Malaysian Health Technology Assessment Section (MaHTAS)