Brain repair mechanisms after cell therapy for stroke.

Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, the underlying mechanisms by which they promote brain repair remain unclear. Here, we briefly review endogenous mechanisms of brain repair after ischaemic stroke and then focus on how different stem and progenitor cell sources can promote brain repair.

Brain transplantation of genetically corrected Sanfilippo type B neural stem cells induces partial cross-correction of the disease.

Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB) is a recessive genetic disorder that severely affects the brain due to a deficiency in the enzyme α--acetylglucosaminidase (NAGLU), leading to intra-lysosomal accumulation of partially degraded heparan sulfate. There are no effective treatments for this disorder. In this project, we carried out an correction of neural stem cells derived from mice (iNSCs) induced pluripotent stem cells (iPSC) using a modified enzyme in which human NAGLU is fused to an insulin-like growth factor II receptor binding peptide in order to improve enzyme uptake.

Advances in Pancreatic Islet Transplantation Sites for the Treatment of Diabetes.

Diabetes is a complex disease that affects over 400 million people worldwide. The life-long insulin injections and continuous blood glucose monitoring required in type 1 diabetes (T1D) represent a tremendous clinical and economic burdens that urges the need for a medical solution. Pancreatic islet transplantation holds great promise in the treatment of T1D; however, the difficulty in regulating post-transplantation immune reactions to avoid both allogenic and autoimmune graft rejection represent a bottleneck in the field of islet transplantation.

Prenatal histological, cellular, and molecular anomalies in trisomy 21 lung.

Down syndrome (DS), also known as trisomy 21 (T21), is the most common human chromosomal anomaly. Although DS can affect many organ systems, lung and heart disease are the leading causes of death. An abundance of existing data suggests that lung abnormalities originate postnatally in DS.

Engineered Biomaterials for Tissue Regeneration of Innervated and Vascularized Tissues: Lessons Learned from the Brain.

Spontaneous healing and recovery of innervated and vascularized tissues are limited. In particular, the complexity of the central nervous system's anatomy, physiology, and pathobiology make efforts to develop effective therapeutic strategies exceptionally challenging. Repairing the brain after injury implies restoring the tissue architecture of the neural and vascular networks both morphologically and functionally.

Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration.

The central nervous system (CNS) plays a central role in the control of sensory and motor functions, and the disruption of its barriers can result in severe and debilitating neurological disorders. Neurotrophins are promising therapeutic agents for neural regeneration in the damaged CNS. However, their penetration across the blood-brain barrier remains a formidable challenge, representing a bottleneck for brain and spinal cord therapy.

Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke.

Stroke is the primary cause of disability due to the brain's limited ability to regenerate damaged tissue. After stroke, an increased inflammatory and immune response coupled with severely limited angiogenesis and neuronal growth results in a stroke cavity devoid of normal brain tissue. In the adult, therapeutic angiogenic materials have been used to repair ischaemic tissues through the formation of vascular networks.

Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability.

Integrin binding to bioengineered hydrogel scaffolds is essential for tissue regrowth and regeneration, yet not all integrin binding can lead to tissue repair. Here, we show that through engineering hydrogel materials to promote α3/α5β1 integrin binding, we can promote the formation of a space-filling and mature vasculature compared with hydrogel materials that promote αvβ3 integrin binding. In vitro, α3/α5β1 scaffolds promoted endothelial cells to sprout and branch, forming organized extensive networks that eventually reached and anastomosed with neighbouring branches.

Injection of Microporous Annealing Particle (MAP) Hydrogels in the Stroke Cavity Reduces Gliosis and Inflammation and Promotes NPC Migration to the Lesion.

With the number of deaths due to stroke decreasing, more individuals are forced to live with crippling disability resulting from the stroke. To date, no therapeutics exist after the first 4.5 h after the stroke onset, aside from rest and physical therapy.

Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R.

Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain.

Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold.

Hydrogels for brain repair after stroke: an emerging treatment option.

Stroke disability is the only major disease without an effective treatment. The substantial clinical burden of stroke in disabled survivors and the lack of a medical therapy that promotes recovery provide an opportunity to explore the use of biomaterials to promote brain repair after stroke. Hydrogels can be injected as a liquid and solidify in situ to form a gelatinous solid with similar mechanical properties to the brain.

Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models.

Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching.

Neuroblast survival depends on mature vascular network formation after mouse stroke: role of endothelial and smooth muscle progenitor cell co-administration.

Pro-angiogenic cell-based therapies constitute an interesting and attractive approach to enhancing post-stroke neurogenesis and decreasing neurological deficit. However, most new stroke-induced neurons die during the first few weeks after ischemia, thus impairing total recovery. Although the neovascularization process involves different cell types and various growth factors, most cell therapy protocols are based on the biological effects of single-cell-type populations or on the administration of heterogeneous populations of progenitors, namely human cord blood-derived CD34(+) cells, with scarce vascular progenitor cells.