Stem cells are cells specialized cell, capable of renewing themselves through cell division and can differentiate into multi-lineage cells. These cells are categorized as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage such as osteocytes, adipocytes and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes). MSCs express cell surface markers like cluster of differentiation (CD)29, CD44, CD73, CD90, CD105 and lack the expression of CD14, CD34, CD45 and HLA (human leucocyte antigen)-DR. hMSCs for the first time were reported in the bone marrow and till now they have been isolated from various tissues, including adipose tissue, amniotic fluid, endometrium, dental tissues, umbilical cord and Wharton's jelly which harbours potential MSCs. hMSCs have been cultured long-term in specific media without any severe abnormalities. Furthermore, MSCs have immunomodulatory features, secrete cytokines and immune-receptors which regulate the microenvironment in the host tissue. Multilineage potential, immunomodulation and secretion of anti-inflammatory molecules makes MSCs an effective tool in the treatment of chronic diseases. In the present review, we have highlighted recent research findings in the area of hMSCs sources, expression of cell surface markers, long-term in vitro culturing, in vitro differentiation potential, immunomodulatory features, its homing capacity, banking and cryopreservation, its application in the treatment of chronic diseases and its use in clinical trials.

Human mesenchymal stem cells - current trends and future prospective

In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.

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Stem cells: past, present, and future.

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

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Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms

Stem cell-based biological tooth repair and regeneration

Pulp necrosis arrests root development in injured immature permanent teeth, which may result in tooth loss. However, dental pulp regeneration and promotion of root development remains challenging. We show that implantation of autologous tooth stem cells from deciduous teeth regenerated dental pulp with an odontoblast layer, blood vessels, and nerves in two animal models. These results prompted us to enroll 40 patients with pulp necrosis after traumatic dental injuries in a randomized, controlled clinical trial. We randomly allocated 30 patients to the human deciduous pulp stem cell (hDPSC) implantation group and 10 patients to the group receiving traditional apexification treatment. Four patients were excluded from the implantation group due to loss at follow-up (three patients) and retrauma of the treated tooth (one patient). We examined 26 patients (26 teeth) after hDPSC implantation and 10 patients (10 teeth) after apexification treatment. hDPSC implantation, but not apexification treatment, led to regeneration of three-dimensional pulp tissue equipped with blood vessels and sensory nerves at 12 months after treatment. hDPSC implantation increased the length of the root (P < 0.0001) and reduced the width of the apical foramen (P < 0.0001) compared to the apexification group. In addition, hDPSC implantation led to regeneration of dental pulp tissue containing sensory nerves. To evaluate the safety of hDPSC implantation, we followed 20 patients implanted with hDPSCs for 24 months and did not observe any adverse events. Our study suggests that hDPSCs are able to regenerate whole dental pulp and may be useful for treating tooth injuries due to trauma.

Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth

Stem cells from human exfoliated deciduous teeth (SHED) have been identified as a novel population of postnatal stem cells capable of differentiating into neural cells, odontogenic cells, and adipocytes. SHED were reported to differentiate into neural cells based on cellular morphology and the expression of early neuronal markers when cultured under neural inductive conditions. This study therefore investigated the therapeutic efficacy of SHED in alleviating Parkinson's disease (PD) in a rat model. We found that SHED could be induced to form neural-like spheres in a medium optimized for neural stem cells in vitro. After incubation with a cocktail of cytokines including sonic hedgehog, fibroblast growth factor 8, glial cell line-derived neurotrophic factor, and forskolin, these SHED-derived spheres further differentiated into a cell population that contained specific dopaminergic neurons. Moreover, transplantation of SHED spheres into the striatum of parkinsonian rats partially improved the apomorphine-evoked rotation of behavorial disorders compared to transplantation of control SHED. Our data indicate that SHED, potentially derived from neural crest cells, may be an optimal source of postnatal stem cells for PD treatment.

Hui Yang

Papers

Stem Cells from Human-Exfoliated Deciduous Teeth Can Differentiate into Dopaminergic Neuron-Like Cells