Mesenchymal stem cells seem too good to believe!

Abstract

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into various cell types including osteoblasts, chondroblasts, adipocytes, vascular smooth muscle cells, and other cell types (Fig. 1). MSCs harbor unique immunomodulatory properties and therefore hold great promise in tissue engineering, since they not only directly participate in tissue regeneration and repair but also modulate the host’s foreign body responses [1]. The signaling pathways regulating MSCs include bone morphogenetic proteins (BMPs), epidermal growth factors (EGF), transforming growth factors (TGF), wingless integration site (wnt) proteins, fibroblastic growth factor (FGF), and transcription factors, and have been reviewed earlier [2]. MSCs can maintain antiinflammatory, anti-fibrotic, antimicrobial, and regenerative properties, so that they could conceivably improve outcomes in various conditions featuring damaged tissues and inflammation [3]. The putative beneficial effects of MSCs include increased cell survival and proliferation, decreased inflammation, and suppression of immune function. With such a broad magical repertoire of effects, how could they miss? Failures have hardly been reported. Could MSCs lower blood pressure or ameliorate hypertension-induced target-organ damage? MSCs have been injected into stroke-prone spontaneously hypertensive rats (SHR). The authors of that report claimed that MSCs had antioxidant and anti-apoptotic effects as well as the ability to repair hippocampal damage in SHR [4]. However, a reduction in blood pressure was not reported. Other investigators injected MSCs into tail veins of rats subjected to 2-kidney, 1-clip renovascular hypertension [5]. MSCs prevented the progressive increase in blood pressure, ameliorated targetorgan damage, reduced fibrosis, proteinuria, and inflammatory cytokines, suppressed the intrarenal renin-angiotensin system, decreased sympathetic hyperactivity, and infiltrated not only the kidneys but also the central nervous system in the rats. These are remarkable claims indeed! Investigators have also applied MSCs to models of renal disease [6, 7]. In this issue of J Mol Med, Hu and colleagues treated Dahl salt-sensitive (S) rats with intrarenal MSCs [8]. Immunohistochemistry and flow-cytometry analyses showed a significantly reduced number of stem cell marker CD133+ cells in the renal medulla of Dahl S rats, compared to controls, suggesting a renal stem-cell deficiency. Rat MSCs or control cells were transplanted into the renal medulla in uninephrectomized Dahl S rats. High-salt diet resulted in sodium retention and hypertension in control Dahl S rats. These effects were significantly attenuated in MSC-treated