Top 3 grants in regenerative medicine: May 2024
This month’s top grants in regenerative medicine, sourced from Dimensions, include projects to decipher the role of immune cells in spinal cord regeneration, enhance fat graft survival using gene therapy-induced vascularization and understand stem cell niche interactions and inter-organ communication during brain regeneration.
Check out this month’s top grants in regenerative medicine:
Deciphering the role of immune cells in spinal cord regeneration
After an injury to the spinal cord, immune cells like microglia and macrophages infiltrate the site of injury and become activated. Depleting these cells in mammals has shown mixed effects post-injury, complicating the identification of the specific immune requirements that promote spinal cord regeneration in mammals.
Unlike mammals, zebrafish can fully regenerate a complete spinal cord injury and, since the zebrafish immune system is conserved in mammals, they provide a useful model to study pro-regenerative immune pathways.
Preliminary data indicates that microglia and macrophages are crucial for spinal cord regeneration in zebrafish, though the specific pathways remain unknown. This research will identify microglia/macrophage-specific cellular identities, gene expression and pathways essential for spinal cord regeneration in zebrafish. Firstly, loss-of-function zebrafish mutants will be used to identify genes crucial for wound healing and restoring immune privilege post-injury. Following this, a human cell culture system will be employed to observe iPSC-derived microglia behavior and test gene function conservation. Finally, lineage tracing will be conducted in zebrafish to determine the origins of pro-regenerative microglia and macrophages post-injury.
Funding amount: US$560,851
Funding period: 1 May 2024 – 30 April 2026
Funder: National Institute of Neurological Disorders and Stroke (MD, USA)
Research organization: Washington University in St Louis (MO, USA)
Enhancing fat graft survival with gene therapy-induced vascularization
Autologous fat grafts have many applications, including in soft tissue reconstruction in cases of oncologic surgery, congenital deformities, traumatic wounds and skin grafts. However, the longevity of these grafts is often poor, largely due to inadequate vascularization of fat after transplantation. Although numerous strategies have been devised to induce angiogenesis and therefore increase the vascularization of transplanted fat, so far none have been translated to human use due to their low potency and bioavailability.
This research aims to test a novel strategy that utilizes gene therapy to induce vascularization and enhance the survival of fat transplants. The gene therapy, Ad5VEGF-All6A+, employs an adenovirus vector expressing a genomic hybrid of 3 major isoforms of human vascular endothelial growth factor (isoforms 121, 165 and 189), a pro-angiogenic growth factor. Ad5VEGF-All6A+ will be administered to harvested human fat, which will then be transplanted into immunodeficient mice. The researchers will investigate if neovascularization and increased survival of the transplant occur.
Funding amount: US$295,901
Funding period: 1 May 2024 – 31 January 2025
Funder: National Heart Lung and Blood Institute (MD, USA)
Research organization: ENYX Therapeutics (NY, USA)
Stem cell niche interactions and inter-organ communication in brain regeneration
The adult brain’s potential to regenerate relies on neural stem cells (NSCs), which are situated in specialized environments, or niches, comprising diverse cells that provide crucial signals and support to the NSCs. The mechanisms by which these niche cells coordinate to activate NSCs for brain repair are not well understood. This research aims to genetically manipulate niche cells in vivo to explore their roles in transitioning NSCs from a dormant state to active proliferation during brain regeneration.
The study will utilize genetically adaptable fruit flies, which have been found to possess NSC-like cells that become active following injury, similar to those in mammals. These niches provide local signals for NSC proliferation and peripheral tissues, such as adipose tissue and the gut, supply the energy required for new cell growth. However, the specific signaling molecules and their sources remain unidentified. The project will examine the communication between the brain and other tissues during the regenerative process.
The goal of this research is to gain a detailed understanding of the interactions within NSC niches and the inter-organ communication that occurs when NSCs are activated after injury. By identifying these molecular and cellular processes, the study aims to advance knowledge in brain regeneration, potentially leading to new developments in regenerative medicine.
Funding amount: US$169,399
Funding period: 1 April 2024 – 31 March 2026
Funder: European Commission (Brussels, Belgium)
Research organization: Champalimaud Foundation (Lisbon, Portugal)
