Therapeutic effects of stem cells from human exfoliated deciduous teeth on diabetic peripheral neuropathy

Abstract

Objective To evaluate the therapeutic potential of stem cells from human exfoliated deciduous teeth (SHED) for diabetic peripheral neuropathy. Methods The biological characteristics of SHED were identified by flow cytometric study and evaluation of differentiation potential. Using high-fat feeding, diabetes was induced in GK rats, and SHED were transplanted into the caudal veins of these rats. Immunohistochemical analysis was used to compare the capillary to muscle fiber ratio and intra-epidermal nerve fiber density between SHED- and saline-treated diabetic rats. Further, the expressions of angiogenesis-related and neurotrophic factors were quantified by real-time PCR and western blot. Results SHED had a capacity of multiple differentiation and shared typical characteristics of mesenchymal stem cells. SHED transplantation relieved diabetic neuropathic pain, enabled functional recovery of the peripheral nerves, and increased the capillary to muscle fiber ratio and intra-epidermal nerve fiber density compared to the saline group and normal controls. Real-time PCR results showed that the expressions of CD31, vWF, bFGF, NGF, and NT-3 in the skeletal muscles were higher in the SHED group than in the saline groups. Western blot results indicated that the levels of the CD31 and NGF proteins were higher in the SHED transplantation group than the saline group. Conclusion SHED transplantation ameliorated diabetic peripheral neuropathy in diabetic GK rats. Thus, systemic application of SHED could be a novel strategy for the treatment of diabetic peripheral neuropathy.

Activation and Biological Properties of Human β Defensin 4 in Stem Cells Derived From Human Exfoliated Deciduous Teeth

“…Cell surface marker analysis by flow cytometry showed that SHED positively expressed mesenchymal stem cell markers, including CD73, CD90, CD105, and CD146, but showed little expression of hematopoietic stem cell markers CD34 and CD45 (Figure 1A and Supplementary Data Sheet S1). The trilineage differentiation ability of SHED we used in the research was proved in our previous work (Xie et al, 2019).…”

Stem Cells from Human Exfoliated Deciduous Teeth Attenuate Trigeminal Neuralgia in Rats

“…Dental-derived mesenchymal stem cells have a strong ability to differentiate into neural, osteogenic, and adipogenic lineages [ 15 – 17 ]. For example, SHED transplantation provided nerve protection by increasing nerve growth factor protein levels and the capillary density in diabetic rats [ 18 ]. Recent studies have revealed that bone marrow stromal cells (BMSCs) reduce the progress of neuropathic pain.…”

“…More importantly, as neural crest cell-associated postnatal stem cells, SHED express various neural cell markers [ 2 ], release key neurotrophic factors, and suppress the apoptosis of astrocytes and neurons [ 7 ]. Importantly, SHED transplantation relieved diabetic peripheral neuropathy and increased the capillary density in diabetic rats [ 18 ]. Therefore, SHED may have advantages over BMSCs in pain control and potentially become an alternative and efficacious treatment for neuropathic pain.…”

Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

“…Genetic animal models of T2DM/DPN (e.g., Bio-Breeding Zucker diabetic rat (BBZDR) /Wor rat, Zucker diabetic fatty (ZDF) rat, Goto Kakizaki (GK) rat, db/db mice, ob/ob mice, diabetic black and tan, brachyuric (BTBR) ob/ob mouse) as well as the streptozotocin (STZ) diabetic rodents (40-80 mg STZ/kg body weight, i.p./i.v.) have been available for years and used to study DPN [30][31][32][33][34][35]. Yet, none follow the gradual onset of metabolic imbalances and the natural progression from obesity to T2DM.…”