Fibrosis is a common feature in most pathogenetic processes in the liver, and usually results from a chronic insult that depletes the regenerative capacity of hepatocytes and activates multiple inflammatory pathways, recruiting resident and circulating immune cells, endothelial cells, non-parenchymal hepatic stellate cells, and fibroblasts, which become activated and lead to excessive extracellular matrix accumulation. The ongoing development of liver fibrosis results in a clinically silent and progressive loss of hepatocyte function, demanding the constant need for liver transplantation in clinical practice, and motivating the search for other treatments as the chances of obtaining compatible viable livers become scarcer. Although initially cell therapy has emerged as a plausible alternative to organ transplantation, many factors still challenge the establishment of this technique as a main or even additional therapeutic tool. Herein, the authors discuss the most recent advances and point out the corners and some controversies over several protocols and models that have shown promising results as potential candidates for cell therapy for liver fibrosis, presenting the respective mechanisms proposed for liver regeneration in each case.

The burden of musculoskeletal disorders (MSK) is increasing worldwide. It affects millions of people worldwide, decreases their quality of life, and can cause mortality. The treatment of such conditions is challenging and often requires surgery. Thus, it is necessary to discuss new strategies. The therapeutic potential of mesenchymal stem cells (MSC) in several diseases has been investigated with relative success. However, this potential is hindered by their limited stemness and expansion ability in vitro and their high donor variability. MSC derived from induced pluripotent stem cells (iPSC) have emerged as an alternative treatment for MSK diseases. These cells present distinct features, such as a juvenile phenotype, in addition to higher stemness, proliferation, and differentiation potential than those of MSC. Here, we review the opportunities, challenges, and applications of iPSC as relevant clinical therapeutic cell sources for MSK disorders. We discuss iPSC sources from which to derive iMSC and the advantages and disadvantages of iMSC over MSC as a therapeutic approach. We further summarize the main preclinical and clinical studies exploring the therapeutic potential of iMSC in MSK disorders.

To analyze therapeutic potential of the conditioned medium from adipose tissue-derived stem cells (ASC) cultivated in 2D (CM-2D) and 3D (CM-3D) models, in mice with Type 1 diabetes (T1D) induced by streptozotocin. Viability andCD105 expression of 2D and 3D ASC were analyzed by flow cytometry. T1D was induced in mice by multiple injections of streptozocin. On the 28th and 29th days after the first injection of streptozocin, diabetic animals received CM-2D or CM-3D. Pancreatic, CM-2D, and CM-3D cytokines were analyzed by cytometric bead array (CBA) and insulin and PDX-1 were observed and quantified by immunohistochemistry. Apoptosis-related proteins were quantified by Western Blotting. ASC in three-dimensional culture released increased levels of IL-6 and IL-2, while IL-4 was decreased. CM-2D induced pancreatic PDX-1 expression and was able to reduce glycemia in diabetic mice one week after injections but not CM-3D. On the other hand, CM-2D and CM-3D were not able to reverse apoptosis of pancreatic cells in diabetic mice nor to increase insulin expression. Together, these results demonstrate that the 3D cell culture secretome was not able to improve diabetes type 1 symptoms at the times observed, while 2D cell secretome improved glycemic levels in T1D mice.