Five subjects experienced durable chimerism, demonstrated immunocompetence and donor-specific tolerance by in vitro proliferative assays, and were successfully weaned off all immunosuppression one

year after transplantation. None of the recipients produced anti-donor antibody or exhibited engraftment syndrome or graft-versus-host disease. These results suggest that manipulation of a mobilized stem cell graft and nonmyeloablative conditioning EGFR antibody represents a safe, practical, and reproducible means of inducing durable chimerism and donor-specific tolerance in solid organ transplant recipients according to the authors. However, in a set-up of dialysis where patients are prone to infections, this proposition does not appear very safe and therefore is not very encouraging. Hence, the search for MSC and now T-regulatory T-cells becomes more intense with rekindled hopes of reaching the promised land of tolerance. In kidney transplantation reperfusion injury can cause tissue destruction leading to low glomerular filtration rate initially and affecting long term function by leading to interstitial fibrosis, which cannot be reversed. MSC have been useful in repair of early tissue injury in animal models of kidney, lung, heart and bowel transplantation.[24]

Remuzzi et al. conducted a pilot trial of intravenous administration of autologous BM-derived MSC on the 7th day of RT in two patients. They found that MSC administration was safe and feasible.[25] Ansari et al. used autologous BM-derived MSC in 30 patients with early chronic kidney diseases (CKD) due to systemic lupus eryrthematosus (SLE) and found significant benefits in RG7422 the form of improved functional status and serum creatinine (SCr) in these patients.[26] Tan et al. conducted a trial using autologous BM-derived MSC in 105 renal transplant (RT) patients. They infused MSC twice,

before anastomosis and 2 weeks after RT. They reported that BM-derived MSC were safe and resulted in better renal function with decreased incidence of infections over one year follow-up.[27] There are ongoing trials in all continents using BM-derived MSC to alleviate tissue injury in autoimmune disorders and transplantation to improve Methocarbamol the long term outcome of grafts. Perico et al. infused autologous MSC 7 days post-renal transplant in two patients who received living related kidneys. These patients received T-cell depletion therapy and were under maintenance immunosuppression of cyclosporin and mycofenolate mofetil and were followed up for about one year. Initially both had rises in serum creatinine; however, at one year, both showed increase in T-regulatory cells (CD4+CD25high FoxP3+ CD127−), with a fall in CD8 + cells and stable graft function.[25] However, barring Ahmedabad group of Trivedi et al. there are no studies available where adipose tissue-derived MSC have been used effectively in inducing and maintaining transplant tolerance.