PBI3 A REVIEW ON PEARLS & PITFALLS OF AUTOLOGOUS BONE MARROW DERIVED MESENCHYMAL STROMAL/STEM CELL THERAPY IN END STAGE LUNG DISEASE; LONGITUDINAL ASSESSMENT OF HEALTH RELATED QUALITY OF LIFE IN THESE PATIENTS

Abstract

Objectives: Lung diseases contribute to a major cause of morbidity & mortality worldwide in current scenario. Though invasive & expensive, lung transplantation (single/double) is a definitive treatment option for End-Stage-Lung-Disease (ESLD) patients who show survival of more than 80% up to year which then drops down to 50% after 3 years. Despite advancements in surgical techniques, complications are inevitable with scarcity of donor lung availability, lung preservation, immunosuppression, management of ischemia/reperfusion, injury, infections, acute & chronic allograft rejection, more commonly called Bronchiolitis Obliterans Syndrome (BOS), which is major impediment to their longtime survival after an year. Thus Autologous Bone-marrow derived Mesenchymal-Stromal/ Stem-Cells (BM-MSCs) therapy emerged as a new frontier in the field of regenerative-medicine to mitigate the symptoms & improve patients HRQOL. They exert immunomodulatory, anti-proliferative & anti-inflammatory effects, circumvenes immune-rejection. It is a non-surgical method with no significant adverse-effects. Based on some preclinical-clinical studies, a few drawbacks which have been proposed for this procedure includes:-stem-cell-ageing, diminished functional capacity, increased senescence during their culture. Methods: The study enrolled subjects of ESLD (n=7) both male & female, aged 40-70 years and have been assessed for safety, feasibility, efficacy of stem-cell procedure & HRQOL in a 6 month follow up period by use of instruments like-SGRQ questionnaire, Modified MRC dyspnoea scale, Borg-Dyspnoea-index, 6 minute walk test, spirometry, diffusing capacity of lung for Carbon-monoxide (DL CO ). Results: The results showed that Autologous-MSC therapy in these patients is free of adverse effects. It was also observed that there has been improvement in these patients condition by way of reduced exacerbations, reduced pathological degeneration, improvement in clinical condition by reduction in duration of Long-Term-Oxygen-Therapy. A few (4) of them have also reported a decline in level of C-reactive-protein thus exhibiting anti-inflammatory-effect of the therapy. Conclusions: Thus,the promising results from above studies show the beneficence of Autologous-BM-MSCs therapy in ESLD patients which indicate that this procedure serves as a potent adjunct along with drug-therapy, thereby increasing the therapeutic-window period for lung transplantation. Nevertheless, several challenges in clinical setting remain to be addressed which include: determining the standard-treatment-protocol of MSCs therapy, their optimal dose, Time, Route-of-administration.