Topical Collection "Stem Cells and Bioengineering for Brain Repair"
Laboratory of Experimental and Clinical Neurosciences, INSERM U-1084, University of Poitiers, CEDEX 9, 86073 Poitiers, France
Interests: cell transplantation; stem cells; biomaterials; iPSC; cortical trauma; Parkinson’s disease; motor behavior; optogenetics
Topical Collection Information
Despite its well-known plasticity, the adult injured brain displays a poor ability to self-repair, whether by generating new cells or long-range connections. Cell transplantation offers a viable treatment strategy for various brain disorders by providing new cells to replace those lost through injury or disease. While significant progress has been made in recent years, the translation of experimental strategies to clinical practice is still limited.
Biomaterials are receiving increased attention in tissue engineering because of their unique and appealing biological properties such as biocompatibility and biodegradability. The combination of cells with biomaterial scaffolds is currently in development and could be a promising approach to enhancing graft survival and functional recovery.
The aim of this Topical Collection is to provide an overview of the current research efforts for the development of therapeutic strategies based on the combination of biomaterial scaffolds, 3D printing, and neurons derived from human embryonic stem cells or induced pluripotent stem cells, to repair neural circuits in the central nervous system after injury.
Dr. Afsaneh Gaillard
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- stem cells
- induced pluripotent stem cells
- brain disorders
- 3D printing
- tissue engineering
- brain repair
Published Papers (3 papers)
Potential Variables for Improved Reproducibility of Neuronal Cell Grafts at Stroke Sites
Viewed by 1191
Interest is growing in using cell replacements to repair the damage caused by an ischemic stroke. Yet, the usefulness of cell transplants can be limited by the variability observed in their successful engraftment. For example, we recently showed that, although the inclusion of
[...] Read more.
Interest is growing in using cell replacements to repair the damage caused by an ischemic stroke. Yet, the usefulness of cell transplants can be limited by the variability observed in their successful engraftment. For example, we recently showed that, although the inclusion of donor-derived vascular cells was necessary for the formation of large grafts (up to 15 mm3
) at stroke sites in mice, the size of the grafts overall remained highly variable. Such variability can be due to differences in the cells used for transplantation or the host environment. Here, as possible factors affecting engraftment, we test host sex, host age, the extent of ischemic damage, time of transplant after ischemia, minor differences in donor cell maturity, and cell viability at the time of transplantation. We find that graft size at stroke sites correlates with the size of ischemic damage, host sex (females having graft sizes that correlate with damage), donor cell maturity, and host age, but not with the time of transplant after stroke. A general linear model revealed that graft size is best predicted by stroke severity combined with donor cell maturity. These findings can serve as a guide to improving the reproducibility of cell-based repair therapies.
Long-Term Evaluation of Intranigral Transplantation of Human iPSC-Derived Dopamine Neurons in a Parkinson’s Disease Mouse Model
Cited by 5
| Viewed by 2899
Parkinson’s disease (PD) is a neurodegenerative disorder associated with loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). One strategy for treating PD is transplantation of DA neuroblasts. Significant advances have been made in generating midbrain DA neurons from human
[...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder associated with loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). One strategy for treating PD is transplantation of DA neuroblasts. Significant advances have been made in generating midbrain DA neurons from human pluripotent stem cells. Before these cells can be routinely used in clinical trials, extensive preclinical safety studies are required. One of the main issues to be addressed is the long-term therapeutic effectiveness of these cells. In most transplantation studies using human cells, the maturation of DA neurons has been analyzed over a relatively short period not exceeding 6 months. In present study, we generated midbrain DA neurons from human induced pluripotent stem cells (hiPSCs) and grafted these neurons into the SNpc in an animal model of PD. Graft survival and maturation were analyzed from 1 to 12 months post-transplantation (mpt). We observed long-term survival and functionality of the grafted neurons. However, at 12 mpt, we observed a decrease in the proportion of SNpc DA neuron subtype compared with that at 6 mpt. In addition, at 12 mpt, grafts still contained immature neurons. Our results suggest that longer-term evaluation of the maturation of neurons derived from human stem cells is mandatory for the safe application of cell therapy for PD.
Better Outcomes with Intranigral versus Intrastriatal Cell Transplantation: Relevance for Parkinson’s Disease
Cited by 4
| Viewed by 2239
Intrastriatal embryonic ventral mesencephalon grafts have been shown to integrate, survive, and reinnervate the host striatum in clinical settings and in animal models of Parkinson’s disease. However, this ectopic location does not restore the physiological loops of the nigrostriatal pathway and promotes only
[...] Read more.
Intrastriatal embryonic ventral mesencephalon grafts have been shown to integrate, survive, and reinnervate the host striatum in clinical settings and in animal models of Parkinson’s disease. However, this ectopic location does not restore the physiological loops of the nigrostriatal pathway and promotes only moderate behavioral benefits. Here, we performed a direct comparison of the potential benefits of intranigral versus intrastriatal grafts in animal models of Parkinson’s disease. We report that intranigral grafts promoted better survival of dopaminergic neurons and that only intranigral grafts induced recovery of fine motor skills and normalized cortico-striatal responses. The increase in the number of toxic activated glial cells in host tissue surrounding the intrastriatal graft, as well as within the graft, may be one of the causes of the increased cell death observed in the intrastriatal graft. Homotopic localization of the graft and the subsequent physiological cell rewiring of the basal ganglia may be a key factor in successful and beneficial cell transplantation procedures.
The below list represents only planned manuscripts. Some of these
manuscripts have not been received by the Editorial Office yet. Papers
submitted to MDPI journals are subject to peer-review.
Title: Potential variables when grafting cells for stroke repair
Authors: Joanna Krzyspiak1,2; Kamran Khodakhah1; Jean M. Hébert1,2,3
Affiliation: 1Department of Neuroscience, Albert Einstein College of Medicine, Bronx, USA 2Stem Cell Institute, Albert Einstein College of Medicine, Bronx, USA 3Department of Genetics, Albert Einstein College of Medicine, Bronx, USA
Title: Effects of hyaluronan-based hydrogel implantation after cortical traumatic injury
Authors: Anaïs Lainé, Sébastien Brot and Afsaneh Gaillard *
Affiliation: Laboratory of Experimental and Clinical Neurosciences, INSERM U-1084, University of Poitiers, 86073 Poitiers cedex 9, France;
* Correspondence: firstname.lastname@example.org
Abstract: Traumatic brain injury leads to a massive death of neurons further to direct lesion but also because of secondary lesions, where neuroinflammation play an important role. We previously reported that a delay between lesion and cell transplantation can enhance graft vascularisation, survival, and projections, and that the modulation of post-traumatic inflammation might be implicated. Biomaterials protecting grafted cells and/or supporting repair processes are currently in development and could be a promising neurorestorative approach. Hyaluronan-based biomaterials are receiving increased attention in tissue engineering because of their unique and appealing biological properties such as biocompatibility and biodegradability. Here, we investigated the therapeutic effect of biomaterial on host tissue after TBI. For this, we implanted it into the motor cortex of adult mice with or without delay after lesion. Soon as one week after, host cortex has integrated and vascularised the biomaterial. This vascularisation, and astrocytes, supports host neuroblasts migration into biomaterial that present a wide phenotype diversity, including oligodendrocytes and neurons. At one month, we have observed a reduction of glial scar around the lesion, a switch towards the pro-regenerative astrocyte phenotype and evidence for anti-inflammatory microglial polarisation. Collectively these results suggest a beneficial effect of biomaterial after a traumatic cortical injury.
Keywords: traumatic brain injury; neuroinflammation, biomaterial; hyaluronan; repair