Nail-Patella syndrome (NPS) is an autosomal dominant disorder that is the result of heterozygous loss-of-function mutations in LMX1B, coding for a LIM homeobox (LIM-HD) transcription factor. Analyses of lmx1b mutant mice have revealed the role of Lmx1b in the development of mesencephalic dopaminergic neurons and the serotonergic system; these areas have been linked with symptoms of attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD). Fifty adults (38 females, 12 males) with NPS completed the Conners’ Adult ADHD Rating Scales—Self-report: Long Version (CAARS) and Beck Depression Inventory-II (BDI-II). The objective was to describe the neurobehavioral phenotype of these subjects and examine possible relationships between neurobehavioral symptoms and NPS. Elevated levels of DSM-IV-TR ADHD Inattentive symptoms were reported on the CAARS by 22% of the NPS sample. The BDI-II Total score was elevated for 40% of the NPS sample. There was a significant increase in the odds of an elevated BDI-II Total score when any of the three CAARS scales were elevated (odds ratios ranging from 11.455 to 15.615). The CAARS and BDI-II did not significantly differ with gender, age, or education level. There was no significant association between genetic mutation-predicted protein status and elevations on CAARS or BDI-II. Individuals with NPS reported co-occurring symptoms of ADHD and MDD, with higher levels of co-occurrence than reported in the literature for the general population. The co-occurrence of these symptoms may be related to mesencephalic dopaminergic neurologic pathway abnormalities that are a consequence of LMX1B loss of function.

Cardiovascular diseases are the leading cause of death worldwide. A completely autologous treatment can be achieved by using elastogenic mesenchymal stem cell (MSC)-derived smooth muscle cells (SMC) at the affected tissue site of vascular diseases such as abdominal aortic aneurysms (AAA). Thus, our work focused on evaluating the efficacy of (a) the combination of various growth factors, (b) different time periods and (c) different MSC lines to determine the treatment combination that generated SMCs that exhibited the greatest elastogenicity among the tested groups using Western blotting and flow cytometry. Additionally, total RNA sequencing was used to confirm that post-differentiation cells were upregulating SMC-specific gene markers. Results indicated that MSCs cultured for four days in PDGF + TGFβ1 (PT)-infused differentiation medium showed significant increases in SMC markers and decreases in MSC markers compared to MSCs cultured without differentiation factors. RNA Seq analysis confirmed the presence of vascular smooth muscle formation in MSCs differentiated in PT medium over a seven-day period. Overall, our results indicated that origin, growth factor treatment and culture period played a major role in influencing MSC differentiation to SMCs.

In this study we examined the potential of muscle derived extracellular matrix (ECM) gel prepared from skeletal muscle as a treatment strategy for acute and chronic degenerative atrophy. We conducted experiments to evaluate the gel’s effectiveness in both a mouse hindlimb unloading (HU) model (disuse atrophy), and on a rabbit shoulder rotator cuff tear (RCT) model (diseased atrophy). In the HU mouse model, the gel enhanced denovo muscle regeneration (4000% higher in centralized nuclei myofiber density) and muscle mass (22% heavier) in the tibialis anterior muscle compared to PBS group. The transcriptomic and proteomic analysis using mouse tissues revealed that the gel elicited adult myogenesis programme. In the RCT rabbit model, the gel enhanced muscle mass (19% heavier), average myofiber cross-sectional area (29% larger), and lowered fatty infiltration (72% less fat) in the supraspinatus muscle compared to repair only. The transcriptomic and proteomic analysis using rabbit tissues revealed that the gel enhanced recovery through promoting a pro-myogenic muscle environment while lessening adipogenesis. The findings suggested that gel injection had a positive effect on the treatment of muscle atrophy and the therapeutic effect of the ECM gel was in part via its impact on fibro-adipogenic progenitor cell behavior, a mechanistic finding that could be exploited for even greater impact.