Cell therapy for kidney injury: different options and mechanisms--mesenchymal and amniotic fluid stem cells

Acute kidney injury (AKI) is emerging as a public health problem in developing and developed countries. It affects up to 7% of hospitalized patients, with a higher prevalence in critical care units. Despite major advances in preventive strategies and support measures, the mortality rate among patients remains higher than 50%. Several pharmacological approaches to improve renal function and survival after an AKI episode have been largely unsuccessful in clinical practice.

Stem cell-based therapy has provided new hopes of innovative interventions to enhance the limited capability of kidney regeneration in AKI. An important target for cell therapy is represented by tubular epithelial cells which after acute ischemic or toxic insults undergo dysfunction and detachment. Among adult stem cells, mesenchymal stromal/stem cells (MSC) are an attractive therapeutic tool by virtue of their unique biological properties, tropism for damaged tissues, and proregenerative capacity. In the present review, we discuss the mechanisms underlying the renoprotective effects of therapies with stem cells of different origins in preclinical models of AKI by evaluating new modalities by which MSC interact with damaged cells via the release of soluble factors and exosomes/microvesicles. Several biological effects, including antiapoptotic, promitogenic, immunomodulatory, and anti-inflammatory activities, have been analyzed in renal tissue of AKI animals receiving stem cell treatments. The mechanisms of stem cell homing and engraftment to sites of tissue damage have also been discussed.

The translation of preclinical data on stem cells into effective and safe new modalities of care is still limited, and further studies are needed before their application in patients with AKI.