Elena Kozlova – Regenerative neurobiology
Our research focuses on regeneration of cells in the nervous system. Our long-term objectives are to
- develop novel therapeutic strategies for neurodegenerative disorders, with particular focus on amyotrophic lateral sclerosis,
- identify microgravity induced cell properties, which might be beneficial for tissue engineering and repair, with particular focus on neural stem cells and insulin producing beta cells, and
- develop 3D bio-printed spinal cord organoids, and neural crest stem cell/beta cell assembloids.
Novel therapeutic strategies for neurodegenerative disorders
Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS) are characterized by the abnormal deposition of aggregates of misfolded proteins, which impair neuronal function and threaten their survival. The pathological aggregates activate immune cells, leading to neuroinflammation, which further compromises neuronal viability and contributes to disease progression.
In our research we focus on ALS, a devastating incurable neurological disorder characterised by progressive motor neuron (MN) death and muscle dysfunction leading, in typical cases, to mean survival time after diagnosis of only 3-5 years. The progression of ALS appears to occur in a prion-like fashion through intercellular transfer of disease driving molecules.
Our recent work indicates that implantation of mesoporous silica particles (MSP) delays disease progression and extends survival in experimental models of ALS, presumably by scavenging disease driving molecules. Our work also indicates that such particles are able to scavenge inflammatory molecules, contributing to ALS, from plasma of ALS patients. In our further studies we aim to determine the efficacy of this scavenging approach and the possibility to tailor mesoporous silica particles to target specific disease associated molecules.
Microgravity induced cell properties for tissue engineering and repair
Understanding how stem cells adapt to space flight conditions is fundamental for human space missions and extra-terrestrial settlement. However, the unique conditions during space flight may also induce the emergence of novel cell properties of interest for biomedicine on the ground.
We have shown that neural crest stem cells that have returned to earth from a short space flight, alter their gene expression towards proliferation and survival compared to cells exposed to microgravity in a ground-based device. We previously showed that this type of neural crest stem cells is of particular interest in regenerative medicine due to their ability to stimulate proliferation and functionality of insulin producing beta cells in vitro and after transplantation in vivo.
To explore this further, we investigate how microgravity in space and on earth affect beta-cell renewal and function cultured alone or together with neural crest stem cells. The results from these studies may contribute to improved cell-based treatment of type 1 diabetes.
3D bio-printed spinal cord organoids and neural crest cell/beta cell assembloids
An organoid is a miniaturized 3D version of an organ produced in vitro, resembling the specific organ in terms of cellular composition and structure. Organoids have emerged as very promising tools for physiological studies, disease modelling and testing of novel, patient adapted therapeutic options.
Organoids have been successfully generated from almost all tissue in the organism, but to create a fully functional organoid of the spinal cord has turned out to be challenging. We use human induced pluripotent stem (iPS) cells embedded in a biocompatible matrix to create a bio-printed spinal cord organoid composed of motor neurons, interneurons and glial cells. We are specifically interested in establishing spinal cord organoids containing neural cells derived from iPS cells of ALS patients to explore novel treatments for this devastating disease.
Combining neural crest stem cells and pancreatic beta cells in a 3D bio-printed assembloid (cells from more than one type of tissue), would allow us to explore the mechanisms underlying the beneficial effect of neural crest stem cells on proliferation and functionality of beta cells.