Table 3.
Cellular therapies using iPSC derivatives
| Disease | Host | Implanted cell type | Mode of implantation | Findings | Ref. |
|---|---|---|---|---|---|
| Multiple sclerosis | Mouse with experimental autoimmune encephalomyelitis | hiPSC neural stem cell | Intraventricular injection (lateral ventricle) | Donor cells localized to lesions. Increased remyelination and motor function. | (Zhang et al. 2016) |
| Progressive multiple sclerosis | Mouse and marmoset | hiPSC-derived oligodendrocytes | Intracerebral injection | Donor cells migrate to lesions and remyelinate axons. | (Thiruvalluvan et al. 2016) |
| Parkinson’s disease | Cynomologous monkey (n = 3, MPTP treated) | Autologous iPSC-derived dopaminergic midbrain neurons | Transplantation into putamen | Case 1: increased motor activity and graft survival. Cases 2 and 3: no improvement, poor graft survival. | (Hallett et al. 2015) |
| Stroke | Sprague Dawley and nude rats post-30 min distal MCA occlusion | hiPSC-derived cortical neuron-fated cells compared with non-fated. | Stereotactic intracerebral transplantation 48 h after MCA occlusion | Migration of cells to lesion. Function improved with cortical neuron-fated donor cells. | (Hallett et al. 2015) |
| Huntington’s disease | Rat with striatal degeneration induced by quinolinic acid | Mouse-derived iPSCs | Intraventricular injection (left lateral ventricle) | Improved learning and memory, increased metabolic activity and size of striatum. Graft differentiated into both neurons and astrocytes. | (Mu et al. 2014) |
| Motor neuron disease | SOD1G39A mice | hiPSC-derived neural stem cells with high aldehyde dehydrogenase activity and expression of integrin VLA4; Positive for LewisX-CXCR4-β1-integrin. | Repeated intrathecal or IV injection | Donor cells migrate and engraft. Improved neuromuscular function, increased spM neurons, and extended survival. Graft inhibited astrocyte activation. | (Nizzardo et al. 2014) (Nizzardo et al. 2016) |
| 12 patients with ALS initial cohort 6 patients with adapted injection device and lumbar stabilization | Fetal neural stem cells | Intraspinal injection | Phase 1 clinical trial. Well-tolerated, targeted to cervical and lumbar spinal cord segments. | (Glass et al. 2012) (Feldman et al. 2014) |