Adult Stem Cell Therapy for Acute Renal Failure: The Hope beyond the Hype?

Acute renal failure (APP) is a complication that occurs frequently in hospitalized patients, and ARF has 50-80% mortality in spite of major advances in intensive care and renal replacement therapy. Stem cells are generally defined as clonogenic cells that are capable of both self-renewal and multi-lineage differentiation. Many experimental animal studies have also showed that cell therapy [bone marrow cells (BMCs), hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs)] might have the potential to rescue animals from organ injuries. Several recent works have demonstrated that repopulation of damaged renal tubules after ARF occurs primarily due to prohferation of surviving tubular epithelial cells and putative renal-specific stem cells, with some contribution of paracrine factors from bone marrow-derived MSCs. When BMCs or HSCs are injected into rodents subjected to ischemic or toxin-induced acute tubular necrosis (ATN), the results with regard to whether they could rescue rodents from ATN are inconsistent. The reasons for the conflicting results of BMC and HSC therapy in ATM are unknown, but they may be due to the different types of cells injected, the number of cells injected, the route of injection, or the injury model of acute renal failure. However, MSCs can contribute to renal tubular regeneration after ATN even though the exact mechanism, either transdifferentiation or effects of paracrinelcytokines (mitogenic, antiapoptotic, anti-inflammatory, angiogenic effects), is uncertain. In the future, the most compelling issue is to determine exactly how MSCs protect the renal tubule from injury, and then to imitate this protective or reparative effect pharmacologically.