Custom-engineered hydrogels for delivery of human iPSC-derived neurons into the injured cervical spinal cord.

Cervical damage is the most prevalent type of spinal cord injury clinically, although few preclinical research studies focus on this anatomical region of injury. Here we present a combinatorial therapy composed of a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. The biomimetic hydrogel has a modular design that includes a protein-engineered component to allow customization of the cell-adhesive peptide sequence and a synthetic polymer component to allow customization of the gel mechanical properties. In vitro studies with encapsulated iPSC-neurons were used to select a bespoke hydrogel formulation that maintains cell viability and promotes neurite extension. Following injection into the injured cervical spinal cord in a rat contusion model, the hydrogel biodegraded over six weeks without causing any adverse reaction. Compared to cell delivery using saline, the hydrogel significantly improved the reproducibility of cell transplantation and integration into the host tissue. Across three metrics of animal behavior, this combinatorial therapy significantly improved sensorimotor function by six weeks post transplantation. Taken together, these findings demonstrate that design of a combinatorial therapy that includes a gel customized for a specific fate-restricted cell type can induce regeneration in the injured cervical spinal cord.

Inflammatory bowel disease in young people: the case for transitional clinics.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is increasing among adolescents. In all, 25% of patients are diagnosed before the age of 16, when they are traditionally transferred from the pediatric to the adult service. METHODS: We conducted a retrospective case-controlled study to characterize patients treated in a novel transitional adolescent-young adult IBD clinic. This compared disease extent, radiation exposure, therapeutic strategy, and requirement for surgery in 100 adolescents with controls from our adult IBD clinic matched for disease duration. RESULTS: The median (range) ages for the adolescent and adult population was 19 (16-28) and 43 (24-84), with a median age at diagnosis of 15 (3-26) and 39 (13-82) respectively (P < 0.001). Crohn's disease was significantly more common in the adolescents. Disease distribution was ileocolonic in 69% of adolescents and 28% of adults, restricted to the ileum in 20% of adolescents and 47% of adults, and colonic only in 11% and 22%, respectively. Upper gastrointestinal involvement occurred in 23% of adolescents, but was not seen in adults (P < 0.01). Total ulcerative colitis was seen in 67% of adolescents and 44% of adults (P < 0.01). Contrary to previous data adolescents did not receive more ionizing radiation than adults. Requirement for immunosuppressive therapy was higher in the adolescent group (53% versus 31%, respectively, P < 0.01). Likewise, 20% of adolescents had required biological therapy compared to only 8% in the adult cohort (P < 0.05). CONCLUSIONS: Gastroenterologists should recognize that IBD is more complex when presenting in adolescence and our data support the creation of specific adolescent transitional clinics.

A female with monosomy 18 mosaicism: a previously undescribed chromosome abnormality.

We report on a patient with monosomy 18 mosaicism, a previously undescribed chromosome abnormality. The phenotype is reminiscent of chromosome 18 ring mosaicism. The reason that the patient survived may be attributed to low level mosaicism for the monosomy.