1. Types of regenerative cells.

Cell type	Source	Rationale	Mechanism of action	Preclinical/clinical results	References
MSC	Human umbilical cord tissue/blood; rodent/human bone marrow	Safe and feasible in phase 1 RCT for bronchopulmonary dysplasia Low immunogenicity (low MHC II), easily obtainable, rapid expansion Autologous/allogeneic administration Paracrine release of trophic factors	Paracrine release of IGF‐1, EGF, VEGF, BDNF Immunomodulatory: regulate T‐cell, B‐cell function, and production of inflammatory cytokines Mitochondrial transfer	Nerve fibre remyelination and axonal regeneration Improve behavioural/motor tests Enhance neural cell proliferation, survival, function Decrease infarct size	Ahn 2016; Boshuizen 2018; Chopp 2002; Hsu 2016; Islam 2012; Liu 2010; Murphy 2013; Park 2016
MNC	Human umbilical cord blood	Readily collected and large supply in cord blood with high plasticity Safe and feasible in phase 1 RCT for hypoxic‐ischaemic encephalopathy Low immunogenicity (minimal HLA matching) Paracrine release of trophic factors Autologous/allogeneic administration	Increase expression of BDNF, NGF, VEGF, GDNF Activation of pro‐survival Akt pathway Decrease TNF‐α and increase IL‐10 gene expression Reduce CD4+ T cell infiltration Regulate hedgehog signalling	Decrease neuronal apoptosis, astrogliosis, inflammation Improve oligodendrocyte survival Induce axonal growth Improve neurobehavioral outcome	Aridas 2016; Cotton 2014; Fan 2005; McDonald 2018; Pimentel‐Coelho 2012; Rowe 2010; Wang 2013
OPC	Rodent/human embryonic stem cell; human NSC derivation	Differentiate into oligodendrocytes (cells highly susceptible to hypoxic‐ischaemic injury) Remyelinate injured axons	Diffuse biodistribution along white matter tracts and differentiate into myelin‐sheath‐producing oligodendrocytes	Promote myelin sheath formation, NSC proliferation, and inhibit apoptosis Motor recovery following CNS injury	Chen 2015; Gopagondanahalli 2016; Kim 2018; Manley 2017; Niimi 2018; Xu 2015
NSC	Human fetal striatum; human ESC; human iPSC	Differentiate into cells necessary for brain repair, including: neurons, astrocytes, and oligodendrocytes Paracrine release of trophic factors Low immunogenicity and tumorigenicity	Immunomodulation Paracrine secretion of BDNF, VEGF, and EGF Attenuate NF‐κB signalling Upregulate glutamate transport	Stimulate survival and migration of endogenous NSCs and neurons Reduce inflammation and reactive oxygen species production Improve axonal growth, motor function, decreased infarct size	Daadi 2016; Huang 2018; Ji 2015; Mine 2013
HSC	Umbilical cord blood	Paracrine release of neurotrophic factors Multipotent capacity and ability to transdifferentiate into neuronal cells Autologous/allogeneic administration	Reduce microglial cells and T lymphocytes Secrete VEGF, HGF, IGF‐1	Decrease infarct size and maintains cerebral blood flow Enhance axonal growth Ameliorate neuronal apoptosis and post‐ischaemic inflammation	Schwarting 2008; Tsuji 2014; Verina 2013
EPC	Human umbilical vein; human umbilical cord blood; human adipose stem cell; human iPSC	Umbilical‐cord‐derived EPCs have higher regenerative potential than adult bone marrow‐derived EPCs Endothelial cell protection, repair, angiogenesis Low immunogenicity Paracrine release of regenerative factors Autologous administration	Anti‐inflammatory effects: reduce CD4+ infiltration to the brain Activation of PI3/Akt pathway Axonal growth: BDNF secretion Angiogenesis: VEGF, IGF‐1 secretion	Improve cognitive and motor function Inhibit neuronal apoptosis Stimulate blood vessel formation and reduce infarct size	Grandvuillemin 2017; Kidani 2016; McDonald 2018; Nabetani 2018; Wang 2016; Wu 2013
iPSC	Skin fibroblasts, umbilical cord tissue, amniotic tissue	Autologous administration Differentiation into multiple neural lineage cells Low immunogenicity	Differentiate into functional neural cells (electrophysiological properties) Decrease infiltration of MPO+ neutrophils and CD11b+ microglia VEGF expression and organelle transfer	Improve survival and sensorimotor function Establish axonal connections Inhibit inflammation, neural apoptosis, and glial scar formation	Cai 2010; Hsu 2016; Oki 2012; Pluchino 2013; Qin 2015; Tornero 2013

BDNF: brain‐derived neurotrophic factor; CNS: central nervous system; ESC: embryonic stem cell; EGF: epidermal growth factor; GDNF: glial cell‐line derived neurotrophic factor; HGF: hepatocyte growth factor; HLA: human leukocyte antigen; HSC: haematopoietic stem cells; IGF‐1: insulin‐like growth factor 1; iPSC: inducible pluripotent stem cells; IL: interleukin; MHC: major histocompatibility complex; MSC: mesenchymal stem cell; MNC: mononuclear cells; NF‐κB: nuclear factor kappa beta; NGF: nerve growth factor; NSC: neural stem cells; OPC: oligodendrocyte progenitor cells; RCT: randomised controlled trial; TNF: tumour necrosis factor; VEGF: vascular endothelial growth factor.