Therapeutic Effects of Mesenchymal Stem Cells for Patients with Chronic Liver Diseases: Systematic Review and Meta-analysis

Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.

A Randomized, Open-Label, Multicenter Trial for the Safety and Efficacy of Adult Mesenchymal Stem Cells after Acute Myocardial Infarction

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9%+/-8.5% vs 1.6%+/-7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105)

Familial Occurrence of Pulmonary Embolism after Intravenous, Adipose Tissue-Derived Stem Cell Therapy

The therapeutic potential of human multipotent mesenchymal stromal cells, especially human adipose tissue-derived stem cells (hASC), is promising. However, there are concerns about the safety of infusion of hASC in human. Recently, we have experienced pulmonary embolism and infarct among family members who have taken multiple infusions of intravenous autologous hASC therapy. A 41-year-old man presented with chest pain for one month. Chest CT showed multiple pulmonary artery embolism and infarct at right lung. Serum D-dimer was 0.8 microg/mL (normal; 0-0.5 microg/mL). He had received intravenous autologous adipose tissue-derived stem cell therapy for cervical herniated intervertebral disc three times (one, two, and three months prior to the visit). His parents also received the same therapy five times and their chest CT also showed multiple pulmonary embolism. These cases represent artificial pulmonary embolisms and infarct after IV injection of hASC. Follow-up chest CT showed spontaneous resolution of lesions in all three patients.

A terapia celular no tratamento da isquemia crítica dos membros inferiores / Cell therapy for the treatment of critical ischemia of the lower limbs

Os autores fazem um histórico sobre as pesquisas com células-tronco embrionárias e do cordão umbilical, suas respectivas vantagens e desvantagens. Seguem com as discussões sobre células-tronco adultas, sua definição, histórico, fontes e participação nos processos de regeneração tecidual, particularmente no endotélio. Ressaltam a importância de fatores que mobilizam as células-tronco adultas a partir da medula óssea: citocinas, angiopoietinas e outros fatores de crescimento. As células-tronco adultas mobilizam-se sob a forma de células endoteliais progenitoras, que têm origem comum com as células endoteliais a partir dos hemangioblastos. Os fatores de mobilização manifestam-se em condições de hipoxia e fazem com que as células endoteliais progenitoras se localizem nos locais de isquemia para produzir a neovasculogênese, que se faz por três possíveis mecanismos: a angiogênese (formação de novos capilares a partir de brotos de capilares já existentes), a arteriogênese (relacionada à circulação colateral) e a vasculogênese (vasos realmente novos). Fazem, a seguir, uma análise da literatura relativa à experimentação animal e aos estudos clínicos. Concluem ressaltando que as células-tronco adultas, embora tenham um grande potencial de uso, ainda demandam muito estudo e pesquisa para se firmar como método terapêutico.