Articular cartilage defect repair is a problem that has long plagued clinicians. Although mesenchymal stem cells (MSCs) have the potential to regenerate articular cartilage, they also have many limitations. Recent studies have found that MSC-derived exosomes (MSC-Exos) play an important role in tissue regeneration. The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix (ACECM) scaffold and to explore the underlying mechanism. The results of in vitro experiments show that human umbilical cord Wharton's jelly MSC-Exos (hWJMSC-Exos) can promote the migration and proliferation of bone marrow-derived MSCs (BMSCs) and the proliferation of chondrocytes. We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype. The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model. This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response, which may be a promoting factor for osteochondral regeneration. In addition, microRNA (miRNA) sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage. We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis. In summary, this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.

We retrospectively investigated outcomes of haploidentical donor (HID) transplant for adults with standard-risk acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) compared with human leucocyte antigen (HLA)-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively (P = 0·020). However, there was no difference in grade III-IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5-year cumulative transplant-related mortality was 16·4%, 11·6% and 19·6% (P = 0·162), the 5-year relapse rate post-transplantation was 14·8%, 21·1% and 16·7% (P = 0·231), the 5-year overall survival was 70·1%, 73·7% and 69·8% (P = 0·525), and the 5-year disease-free survival was 68·7%, 67·3% and 63·7%, respectively (P = 0·606). Furthermore, the 3-year GVHD-free, relapse-free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard-risk adults with ALL in CR1 who lack matched donors.

Background and Purpose Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke, but little is known about its epidemiology. We studied the prevalence of ICAS and its association with vascular risk factors using high resolution magnetic resonance angiography (MRA) in a U.S. cardiovascular cohort. Methods The Atherosclerosis Risk in Communities (ARIC) study recruited participants from four U.S. communities from 1987-1989. Using stratified sampling, we selected 1980 participants from visit-5 (2011-2013) for high resolution 3T-MRA. All images were analyzed in a centralized lab and ICAS was graded as — no stenosis, <50% stenosis, 50-69% stenosis, 70-99% stenosis and complete occlusion. We calculated per-vessel and per-person prevalence of ICAS (weighted for n=6,538 visit-5 participants), and also estimated the U.S. prevalence. We used multivariable logistic regression to identify variables independently associated with ICAS. Results Subjects who had an adequate MRA (n=1765) were aged 67-90 years, 41% were men, 70% were white and 29% were African-American. ICAS was prevalent in 31% of participants and 9% had ICAS ≥50%. Estimated U.S. prevalence of ICAS≥50% for 65-90 years old was 8% for Whites and 12% for African-Americans. Older age, African-American race, higher systolic blood pressure, and higher low density lipoprotein cholesterol levels were associated with increased odds of ICAS, while higher levels of high density lipoprotein cholesterol and use of cholesterol lowering medications were associated with decreased odds of ICAS. Body mass index and smoking were not associated with ICAS. Conclusion The prevalence of ICAS in older adults is high, and could be a target for primary prevention of stroke and dementia in this population.