The conventional intravascular administration of mesenchymal stem cells (MSCs) leads to the low persistence of cells and a shortened therapeutic window. Now, researchers led by Biju Parekkadan (Rutgers University, Piscataway, NJ, USA) describe the immobilization of MSCs within an ex vivo drug delivery device that circulates the patient's blood akin to a dialysis procedure. In their recent STEM CELLS Translational Medicine study, Swaminathan et al. report the first use of this technology in human patients with acute kidney injury (AKI). Overall, the data from this phase I/II trial support the therapeutic hypothesis that ex vivo delivery of MSC-secreted factors leads to immunomodulation, reprogramming of immune cells, and subsequent protection of kidney injury.

Treating neurological disorders remains a challenge due to the implication of multifactorial, complex etiologies. In recent years, the therapeutic benefits of the intranasal administration of extracellular vesicles isolated from mesenchymal stem cells (MSC-EVs) have gained attention. Extracellular vesicles retain the advantages of their parental cells, while intranasal administration provides a non-invasive method to bypass the blood-brain barrier and target specific pathological regions. In a recent STEM CELLS review article, researchers led by Daniel Offen (Tel Aviv University, Israel) summarize the current status of research into MSC-EVs administrated via the intranasal pathways and the potential of this promising therapeutic approach.

Parkinson's disease is a major neurodegenerative disease and how the lack of dopamine affects neurogenesis in the ventricular-subventricular zone (V-SVZ) remains unclear. In a new STEM CELLS article, researchers led by José Luis Labandeira-Garcia and Jannette Rodríguez-Pallares (Universidade de Santiago de Compostela, Spain) show that dopamine increases proliferation and generation of neuroblasts in the V-SVZ and that the blockade of angiotensin AT2 receptors suppresses these effects, showing a functional dependence between dopamine and the renin-angiotensin system (RAS). More importantly, Garcia-Garrote et al. establish that the blockade of angiotensin AT1 receptors or stimulation of angiotensin AT2 receptors can counteract the decline in neurogenesis observed in the V-SVZ in animal models of Parkinson's disease.

Human mesenchymal stem cell (MSC) therapy represents a potentially exciting treatment choice for disorders resulting from an inflammatory/heightened immune response. In a new STEM CELLS Translational Medicine study from the labs of Carl A. Gregory and Roland Kaunas (Texas A&M Health Science Center, Bryan, TX, USA), researchers report on their studies regarding the therapeutic development of induced pluripotent stem cell-derived MSCs (iPSC-MSCs) Rogers et al. established procedures for the manufacture of iPSC-MSCs attached to novel digestible microcarriers in scalable bioreactors that permitted rapid harvest at high yields and viability. Overall, this study represents the first description of a robust, scalable, and cost-effective method for generating human iPSC-MSCs, which represents a significant contribution to their translational potential. Image - Osteogenic and adipogenic differentiation potential after RWVB expansion on GelMA microcarriers.