Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis

Hirata, Marina; Ishigami, Masatoshi; Matsushita, Yoshihiro; Ito, Takanori; Hattori, Hiroyuki; Hibi, Hideharu; Goto, Hidemi; Ueda, Minoru; Yamamoto, Akihito

doi:10.5966/sctm.2015-0353

Cited by 60 publications

(49 citation statements)

References 67 publications

(70 reference statements)

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“…Dental pulp stem cells secrete a broad repertoire of trophic and immunomodulatory factors that have the potential to treat various types of intractable diseases [22][23][24][25][26][36][37][38][39][40][41]. We previously showed that the factors in SHED-CM improve PNI in a rat model of sciatic nerve transection; however, the mechanisms involved in repairing the damaged nerve have been elusive.…”

Section: Discussionmentioning

confidence: 99%

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity

et al. 2016

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Peripheral nerves (PNs) exhibit remarkable self-repairing reparative activity after a simple crush or cut injury. However, the neuronal transection involving a nerve gap overwhelms their repairing activity and causes persistent paralysis. Here, we show that an implantation of the serum-free conditioned medium from stem cells from human exfoliated deciduous teeth (SHED-CM) immersed in a collagen sponge into the nerve gap formed by rat facial nerves transection restored the neurological function. In contrast, SHED-CM specifically depleted of a set of anti-inflammatory M2 macrophage inducers, monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9) lost the ability to restore neurological function in this model. Notably, the combination of MCP-1 and sSiglec-9 induced the polarization of M2 macrophages in vitro, resulting in the expression of multiple trophic factors that enhanced proliferation, migration, and differentiation of Schwann cells, blood vessel formation, and nerve fiber extension. Furthermore, the implantation of a collagen graft containing MCP-1/sSiglec-9 into the nerve gap induced anti-inflammatory M2 macrophage polarization, generated a Schwann-cell bridge instead of fibrotic scar, induced axonal regrowth, and restored nerve function. The specific elimination of M2 macrophages by Mannosylated-Clodrosome suppressed the MCP-1/sSiglec-9-mediated neurological recovery. Taken together, our data suggest that MCP-1/sSiglec-9 regenerates PNs by inducing tissue-repairing M2 macrophages and may provide therapeutic benefits for severe peripheral nerve injuries. Stem Cells 2017;35:641-653.

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Section: Discussionmentioning

confidence: 99%

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity

et al. 2016

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“…Taken together, it is considered that both neural differentiation and paracrine mechanism are responsible for SHED‐induced therapeutic potential for contused spinal cord injury. Likewise, it has been demonstrated that SHED transplantation ameliorate liver fibrotic disfunction via integrated actions of both direct hepatocyte differentiation and indirect paracrine mechanism‐mediated antifibrosis and anti‐inflammation potentials . Consequently, in terms of mechanisms underlying PSC transplantation‐derived benefits, it is important to note that paracrine mechanism initiated by therapeutic factors secreted from transplanted PSCs, at least partially, participates in treatment and enhances endogenous tissue repair capability.…”

Section: Introductionmentioning

confidence: 99%

Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications

Shi

Mao

Liu

2020

Stem Cells Translational Medicine

134

128

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Human pulp stem cells (PSCs) include dental pulp stem cells (DPSCs) isolated from dental pulp tissues of human extracted permanent teeth and stem cells from human exfoliated deciduous teeth (SHED). Depending on their multipotency and sensitivity to local paracrine activity, DPSCs and SHED exert therapeutic applications at multiple levels beyond the scope of the stomatognathic system. This review is specifically concentrated on PSC‐updated biological characteristics and their promising therapeutic applications in (pre)clinical practice. Biologically, distinguished from conventional mesenchymal stem cell markers in vitro, NG2, Gli1, and Celsr1 have been evidenced as PSC markers in vivo. Both perivascular cells and glial cells account for PSC origin. Therapeutically, endodontic regeneration is where PSCs hold the most promises, attributable of PSCs' robust angiogenic, neurogenic, and odontogenic capabilities. More recently, the interplay between cell homing and liberated growth factors from dentin matrix has endowed a novel approach for pulp‐dentin complex regeneration. In addition, PSC transplantation for extraoral tissue repair and regeneration has achieved immense progress, following their multipotential differentiation and paracrine mechanism. Accordingly, PSC banking is undergoing extensively with the intent of advancing tissue engineering, disease remodeling, and (pre)clinical treatments.

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“…90 Similarly, adipose-derived stem cells (ASC) are transplanted after reconstructive surgery after tumor ablation. 91 Similarly, a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) resulted in fibrotic scar resolution.…”

Section: Use Of Tissue Specific Stem Cellsmentioning

confidence: 99%

“…91 Induced pluripotent stem cells (iPSCs) are also used as diagnostic and potentially therapeutic tools to study occurrence of model disease and assess the toxicity of pharmaceutical medications. 92 These are also used for production of autologous stem cells from terminally differentiated somatic cells.…”

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confidence: 99%

Role of Biological Scaffolds, Hydro Gels and Stem Cells in Tissue Regeneration Therapy

Upadhyay¹

2017

ATROA

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Present review article emphasizes role of biological scaffolds, hydrogels and stem cells in tissue engineering mainly in regeneration or repairing of damaged tissues. Highly porous scaffold biomaterials are developed which act as templates for tissue regeneration and potentially guide the growth of new tissue. Present article also describes de-cellularization, cell printing, vascularization, integration of cross linking of methods for scaffolding of biomaterials to reproduce and recapitulate complexity in engineered tissues. It also explains different scaffold types, polymer hydrogels which are necessary for formation of microstructure, cell attachment, differentiation, tissue vascularization and integration. It also explains use of induced pluripotent stem cells (iPSCs) and engineered MSCs as new diagnostic and potential therapeutic tools to remove sustained damage and complications from organ failures. These engineered MSCs assist in making self-assembling supramolecular hydrogels, which have larger applications in cell therapy of intractable diseases and tissue regeneration. No doubt development of more advanced biomaterials, growth factors and stem cell derived products/factors and tissue transplantation methods based on cell regeneration programming will revolutionize the clinical therapeutics. This article suggests identification of new biomaterials/biomolecules such as growth factors, scaffolds, integration, adhesion and regulatory molecules and cell secreted factors which can induce major metabolic and signaling pathways during phase of tissue repairing and induction of regeneration. This innovative research area needs many conceptual improvements in organ therapies, methods and technological advancement to scale more services to the human society.

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Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis

Cited by 60 publications

References 67 publications

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity

Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity

Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications

Role of Biological Scaffolds, Hydro Gels and Stem Cells in Tissue Regeneration Therapy

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