apr
Raquel Martínez Curiel- Institutionen för kliniska vetenskaper, Lund
Title: Stem Cell Therapy for Ischemic Stroke
Main supervisor: Zaal Kokaia
Reviewers: Daniella Rylander Ottosson and Martin Garwicz
Abstract
Background
Ischemic stroke represents 85% of the cases, and it is caused by a shortage of glucose and oxygen in a specific brain area, leading to the death of different cell types, such as neurons and oligodendrocytes. Neuronal death is the main cause of motor and cognitive impairments observed in patients. Apart from mechanical and pharmacological removal of the thrombus applied only during the first hours, there’s no effective treatment to improve functional recovery. Therefore, replacing these neural cells is essential for the functional recovery of patients. Currently, the clinical trials based on stem cell transplantation performed in stroke patients have not aimed at cellular replacement, but instead, they have been shown to exert a bystander effect.
Preliminary results
We have demonstrated the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line. This cell line also gives rise to neurons with the capacity to integrate into stroke-injured adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin sheathing around human axons in the host tissue after grafting onto adult human cortical organotypic cultures.
We have also described a rapid and efficient protocol for generating cortical neurons via direct programming of human embryonic stem (hES) cells. Our results show that 7 days of overexpression of the transcription factor neurogenin 2 (NGN2) in vitro generates hES- induced cells with cortical phenotype, as revealed by immunocytochemistry and RT- qPCR, and electrophysiological properties of neurons in an intermediate stage of maturity. Three months after transplantation into the stroke-injured rat cortex, the hES- induced neurons (hES-iNs) showed immunocytochemical markers of mature layer- specific cortical neurons. They sent widespread axonal projections to several areas in both hemispheres of the host brain. Their axons became myelinated and formed synaptic contacts with host neurons, as shown by immunoelectron microscopy.
Our findings support the potential future use of human PSC-derived cell lines to promote effective clinical recovery following brain injuries.
Any published articles should be listed after the abstract
Martinez-Curiel, R., Jansson, L., Tsupykov, O., Avaliani, N., Aretio-Medina, C., Hidalgo, I., Monni, E., Bengzon, J., Skibo, G., Lindvall, O., Kokaia, Z., Palma-Tortosa, S. Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons, Stem Cell Reports (2023), https://doi.org/10.1016/j.stemcr.2023.04.010
Palma-Tortosa, S., Martínez-Curiel, R., Aretio-Medina, C., Avaliani, N., Kokaia, Z. Organotypic Cultures of Adult Human Cortex as an Ex vivo Model for Human Stem Cell Transplantation and Validation. J. Vis. Exp. (190), e64234, doi:10.3791/64234 (2022).
Martinez-Curiel, R., Hayj, M., Tsupykov, O., Jansson, L., Avaliani, N., Coll-San Martín, B., Monni, E., Skibo, G., Lindvall, O., Palma-Tortosa, S., Kokaia, Z. Human cortical neurons rapidly generated by direct ES cell programming integrate into stroke-injured rat cortex. BioRxiv (2024)
Om evenemanget
Plats:
B10 Seminar Room
Kontakt:
raquel [dot] martinez_curiel [at] med [dot] lu [dot] se