TABLE 1.
Summary of the studies exploring cell replacement occurrence in stem cell therapy for brain damage (organized in chronological order).
| References | Cell source | Damage model | Specie | Injection site | Description |
| Michelsen et al. (2015) | Mouse ESC | Cortical ablation with ibotenic acid | Mouse | Visual cortex | Appropriate cortical area identity of grafted neurons is essential for correct reconstruction of adult damaged cortical circuitry |
| Falkner et al. (2016) | Mouse Fetal | Cortical ablation with chlorine e6 | Mouse | Visual cortex | Neocortical grafted cells integrate structurally and functionally into the adult cortical circuitry |
| Doerr et al. (2017) | Human ESC | No lesion | Mouse | Hippocampus and Striatum | Innervation network developed by grafted cells is similar to the one generated by endogenous neurons, being determinant the area where the cells are transplanted |
| Tornero et al. (2017) | Human iPSC | Cortical ischemic stroke | Rat | Sensorimotor cortex | Grafted neurons integrate in stroke-injured brain and receive functional afferent inputs from host neurons that are activated by sensory stimuli |
| Somaa et al. (2017) | Human ESC | Focal Ischemia with endothelin-1 | Rat | Sensorimotor cortex | Hydrogels fabricated with peptides for laminin-derived epitope improve differentiation and enhance synaptic connectivity of human ESC-derived cortical neurons grafted after stroke |
| Green et al. (2018) | Human ESC | Cortical ischemic stroke | Mouse | Sensorimotor cortex | Grafted neurons stabilize stroke-damaged functional neuronal networks through paracrine effects |
| Terrigno et al. (2018) | Mouse ESC | No lesion/Ischemic lesion | Mouse | Cortex and Hippocampus | Identity of grafted neuronal precursors determine its connectivity and integration after transplantation in cortex or striatum |
| Espuny-Camacho et al. (2018) | Mouse ESC | Cortical ablation with ibotenic acid | Mouse | Visual cortex | Grafted neurons with visual identity display similar functional and morphological features from the host neurons and establish a similar projection pattern |
| Nisbet et al. (2018) | Human ESC | Focal Ischemia with endothelin-1 | Rat | Sensorimotor cortex | Peptide-based hydrogels loaded with BDNF increase long-term survival and vascularization of grafted ESC-derived cortical neurons while reducing secondary degeneration |
| Vogel et al. (2019) | Human iPSC | No lesion | Mouse | Cortex | In vivo luminescence imaging of grafted cells is an effective tool to monitor cell differentiation and to detect its spontaneous differentiation into astrocytes and mature neurons |
| Yu et al. (2019) | Mouse iPSC | Cortical ischemic stroke | Mouse | Sensorimotor cortex | Optochemogenetic stimulation of grafted cells improve rescue of neural network lost connectivity and function after stroke |
| Linaro et al. (2019) | Human ESC | No lesion | Mouse | Lateral ventricles | Graft-derived cortical neurons integrate in host neuronal network and combine intrinsic human development with host-like activity pattern |
| Palma-Tortosa et al. (2020) | Human iPSC | Cortical ischemic stroke | Rat | Sensorimotor cortex | Graft-derived cortical neurons send transcallosal projections to the contralateral hemisphere and generate functional synapses with host neurons contributing to behavioral improvements |
| Andreoli et al. (2020) | Rat Fetal | Cortical ablation with DT system | Rat | Sensorimotor cortex | Graft-derived neurons form vascularized clusters that integrate into host circuitry and survive long-term, leading to functional recovery |
| Xiong et al. (2021) | Human ESC | Parkinson Disease | Mouse | Substantia nigra/Striatum | Graft-derived neurons resemble host ones and its projection pattern depends on intrinsic cell properties. These cells repair nigro-striatal lesioned circuit restoring circuit functionality |
ESC, embryonic stem cell; iPSC, induced pluripotent stem cell; DT, Diphtheria toxin; BDNF, brain-derived neurotrophic factor.