A bioprinted 3D gut model with crypt-villus structures to mimic the intestinal epithelial-stromal microenvironment.

The intestine is a complex tissue with a characteristic three-dimensional (3D) crypt-villus architecture, which plays a key role in the intestinal function. This function is also regulated by the intestinal stroma that actively supports the intestinal epithelium, maintaining the homeostasis of the tissue. Efforts to account for the 3D complex structure of the intestinal tissue have been focused mainly in mimicking the epithelial barrier, while solutions to include the stromal compartment are scarce and unpractical to be used in routine experiments. Here we demonstrate that by employing an optimized bioink formulation and the suitable printing parameters it is possible to produce fibroblast-laden crypt-villus structures by means of digital light projection stereolithography (DLP-SLA). This process provides excellent cell viability, accurate spatial resolution, and high printing throughput, resulting in a robust biofabrication approach that yields functional gut mucosa tissues compatible with conventional testing techniques.

Generation and Evaluation of Novel Stromal Cell-Containing Tissue Engineered Artificial Stromas for the Surgical Repair of Abdominal Defects.

Repair of abdominal wall defects is one of the major clinical challenges in abdominal surgery. Most biomaterials are associated to infection and severe complications, making necessary safer and more biocompatible approaches. In the present work, the adequate mechanical properties of synthetic polymer meshes with tissue-engineered matrices containing stromal mesenchymal cells is combined to generate a novel cell-containing tissue-like artificial stroma (SCTLAS) for use in abdominal wall repair. SCTLAS consisting on fibrin-agarose hydrogels seeded with stromal cells and reinforced with commercial surgical meshes (SM) are evaluated in vitro and in vivo in animal models of abdominal wall defect. Inflammatory cells, collagen, and extracellular matrix (ECM) components are analyzed and compared with grafted SM. Use of SCTLAS results in less inflammation and less fibrosis than SM, with most ECM components being very similar to control abdominal wall tissues. Cell migration and ECM remodeling within SCTLAS is comparable to control tissues. The use of SCTLAS could contribute to reduce the side-effects associated to currently available SM and regenerated tissues are more similar to control abdominal wall tissues. Bioengineered SCTLAS could contribute to a safer treatment of abdominal wall defects with higher biocompatibility than currently available SM.

Comment: CAPN10 alleles are associated with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation infertility, hyperandrogenemia, and frequently insulin resistance. This study investigated whether polymorphisms in the CAPN10 gene are related with PCOS etiology. The allelic frequencies and genotypes of CAPN10 polymorphisms UCSNP-44, 43, 19, and 63 were determined in 55 well characterized women with polycystic ovaries and 93 unrelated healthy controls using spectrofluorimetric analyses and real-time PCR. Our data indicate that CAPN10 UCSNP-44 allele is associated with PCOS in the Spanish population (P = 0.01). These results support a role of Calpain 10 gene in PCOS susceptibility in humans.

Specific CAPN10 gene haplotypes influence the clinical profile of polycystic ovary patients.

Recently, several research groups have evaluated CAPN10 gene in polycystic ovarian syndrome (PCOS) patients and other phenotypes, including hirsutism or intermediate phenotypes of PCOS. Molecular genetic analysis of CAPN10 gene indicates that different alleles may play a role in PCOS susceptibility and could be associated with idiopathic hirsutism. However, these observations are not exempt from controversy, because independent studies cannot replicate these preliminary findings. We present a haplotype-phenotype correlation study of CAPN10 haplotypes in 148 women showing ecographically detected polycystic ovaries (PCO) combined with one or more of these clinical symptoms: amenorrhea or severe oligomenorrhea, hyperandrogenism, and anovulatory infertility, as well as 93 unrelated controls. We have reconstructed and analyzed 482 CAPN10 haplotypes in patients and controls. We detected the association of UCSNP-44 allele with PCO phenotype in the Spanish population (P = 0.02). In addition, we identified several CAPN10 alleles associated to phenotypic differences observed between PCO patients, such as the presence of hypercholesterolemia (haplotype 1121, P = 0.005), presence of hyperandrogenic features (P = 0.05), and familial cancer incidence (haplotype 1111, P = 0.0005). Our results confirm the association of UCSNP-44 allele with PCO phenotype in the Spanish population. Moreover, we have identified novel candidate risk alleles and genotypes, within CAPN10 gene, that could be associated with important phenotypic and prognosis differences observed in PCOS patients.