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BackgroundMotor aphasia, which can affect the communication ability of patients and even triggers severe psychological disorders, is one of the most common sequelae after stroke. Acupuncture (a typical complementary alternative therapy) is frequently combined with speech training (ST) to treat post-stroke motor aphasia (PSMA) and presents significant efficacy. However, the most effective acupuncture intervention is still unknown. This study aims to analyze the efficacy of several acupuncture approaches combined with ST for PSMA to identify the best intervention for clinical decision-making by using network meta-analysis (NMA).MethodsEight major databases were searched from the time of their establishment to March 2022. Clinical efficacy rate (CER) was used as the primary outcome indicator. R software (version 4.13.0) and STATA software (version 16.0) were used to analyze the data.ResultsA total of 29 randomized controlled trials (RCTs) and six treatment regimens were included in this study. In the pair-wise meta-analysis, we found that the efficacy of scalp-tongue acupuncture (STA) combined with ST [OR = 8.30; 95% Credible interval (CrI): 3.87, 17.33], tongue acupuncture (TA) combined with ST (OR = 3.95; 95% CrI: 2.27, 6.89), scalp-body acupuncture (SBA) combined with ST (OR = 3.75; 95% CrI: 2.26, 6.22), scalp acupuncture (SA) combined with ST (OR = 2.95; 95% CrI: 1.74, 5.0), and body acupuncture (BA) combined with ST (OR = 2.30; 95% CrI: 1.26, 4.19) were significantly superior to that of ST. In addition, the efficacy of STA + ST was significantly superior to that of SA +ST (OR = 2. 82; 95% CrI: 1.24, 6.38) and BA + ST (OR = 3.61; 95% CrI: 1.40, 9.29). According to the surface under the cumulative ranking curve (SUCRA), STA + ST (SUCRA = 97.9%) may be the best treatment regimen to improve the clinical outcome in patients with PSMA.ConclusionThe NMA showed that STA combined with ST may be the best treatment to improve CER, compared with other combination treatments. However, since the overall quality and number of studies are limited, further RCTs with a large sample and multicenter are needed for further validation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=316081, identifier CRD42022316081.

Acute liver failure (ALF) is a life-threatening disease that occurs secondary to drug toxicity, infection or a devastating immune response. Orthotopic liver transplantation and hepatocyte transplantation are effective treatments but are limited due to the shortage of donor organs, the requirement for life-long immune suppression and surgical challenges. Stem cell transplantation is a promising alternative therapy for fulminant liver failure owing to the immunomodulatory abilities of stem cells. Human endoderm stem cells (hEnSCs) are germ layer-specific, self-renewable and nontumorigenic cells derived from pluripotent stem cells. Here, we report that hEnSCs transplanted into the liver are able to effectively reverse hepatic injury in rodent and swine ALF models. We demonstrate that hEnSCs tune the local immune microenvironment by skewing macrophages/Kupffer cells towards an anti-inflammatory state and by reducing inflammatory T helper cells. Single-cell transcriptomic analyses of infiltrating and resident monocytes/macrophages isolated from animal livers revealed dramatic changes, including changes in gene expression that correlated with the activation state, and dynamic population heterogeneity among these cells after hEnSC transplantation. We further demonstrate that hEnSCs modulate the activation state of macrophages/Kupffer cells via cystatin SN (CST1)-mediated inhibition of interferon signaling. hEnSC transplantation represents a novel and powerful cell therapeutic treatment for ALF.

The ever-increasing therapeutic and pharmaceutical demands for liver cells and tissues call for mass production systems that enable efficient in vitro generation of hepatic cell lineages. Here, we describe the use of human endoderm stem cells (EnSCs) as precursors for generating hepatoblasts, as well as functionally mature and transplantable hepatocytes or cholangiocytes in a large-scale serum-free 3D differentiation system. Single-cell transcriptomic analysis is used as a tool to characterize the hepatic populations and guide improvements to the protocol. We demonstrate that the hepatic differentiation of EnSCs recapitulates the in vivo developmental trajectory and find that the regulation of the EGF and MAPK signaling pathways is important for proper lineage progression for the generation of functionally mature hepatocytes or cholangiocytes. When transplanted into liver disease animal models, the resultant hepatocytes are able to rescue the animals and repopulate the host livers. The establishment of this large-scale system for hepatic differentiation of EnSCs lays the foundation for cell-based therapeutic applications for liver diseases and for in vitro liver reconstruction.

Transplantation of human hepatocytes (HHs) holds significant potential for treating liver diseases. However, the supply of transplantable HHs is severely constrained by limited donor availability and compromised capacity for in vitro expansion. In response to chronic injury, some HHs are reprogrammed into proliferative cells that express both hepatocyte and progenitor markers, suggesting exploitable strategies for expanding HHs in vitro. Here, we report defined medium conditions that allow 10,000-fold expansion of HHs. These proliferating HHs are bi-phenotypic, partially retaining hepatic features while gaining expression of progenitor-associated genes. Importantly, these cells engraft into injured mouse liver at a level comparable to primary HHs, and they undergo maturation following transplantation in vivo or differentiation in vitro. Thus, this study provides a protocol that enables large-scale expansion of transplantable HHs, which could be further developed for modeling and treating human liver disease.