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Table 2 Main studies on stem cell therapy in NEC

From: Stem cell therapy as a promising strategy in necrotizing enterocolitis

Stem cell type (location)

Main mechanisms

Benefits

Limitations

References

ISCs (Base of intestinal crypts)

Paracrine; other signaling pathways

Regulate intestinal microbiota, mucosal immune response, inflammatory cytokines and cell apoptosis

Over-reliance on the balance between proliferation and differentiation

Kandasamy et al. (2014)

BM-MSCs (Bone marrow)

Paracrine trophic factors; prolyl hydroxylase 2 silencing

Notably decrease inflammation; improve tissue pathology

Low proliferative ability; effect is affected by donor age

McCulloh et al. (2017b), Weil et al. (2009), Chen et al. (2020), Alves et al. (2012), Kagia et al. (2019), Li et al. (2018)

AF-MSCs (Amniotic fluid)

COX-2; Wnt; ER stress

Easy to cultivate; enhance clinical translation; prevent ascites; prolong survival; low tumorigenicity

Few clinical trials to assess the safety

McCulloh et al. (2017b), Jensen et al. (2016), Rosner and Hengstschläger (2021), Zani et al. (2014b)

UC-MSCs (Umbilical cord/umbilical cord blood)

Nitric oxide synthase; hydrogen sulfide

Notably decrease inflammation; improve tissue pathology

Uncertainty of abnormal long-term development

McCulloh et al. (2017b), Jensen et al. (2018), Drucker et al. (2019), Kagia et al. (2019), Prather et al. (2008)

P-MSCs (Placenta)

Wnt; paracrine effects

Good availability; few ethical problems

Few clinical trials to assess the safety

Weis et al. (2021), Duan et al. (2020), Khalifeh Soltani et al. (2019)

NSCs (Intestine/amniotic fluid)

ENS; neuronal nitric oxide synthase

Reduce immunological rejection by autologous transplantation; improve intestinal motility

Difficult to separate and cultivate; ineffective IP injection; little improvement in inflammation

Burns and Thapar (2014), McCulloh et al. (2017b), Kagia et al. (2019), Nitkin et al. (2020)

  1. ISCs intestinal stem cells; MSCs mesenchymal stem cells; BM bone marrow; AF amniotic fluid; COX-2 cyclooxygenase-2; ER endoplasmic reticulum; UC umbilical cord; P placenta; NSCs neural stem cells; ENS enteric nervous system; IP intraperitoneal