Transplantation of human dental pulp stem cells promotes peripheral nerve regeneration after sciatic nerve injury in rats
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic resource for the peripheral nervoussystem (PNS) and central nervous system (CNS) that is attributable to their capacity for neuronal differentiation. Human dental pulp stem cells (hDPSCs), which exhibit MSC-like traits, can differentiate into neuron-like cellsand secrete critical neurotrophic factors; however, their therapeutic potential in peripheral nerve injury remainsunexplored. This study investigated the regenerative effects of hDPSC transplantation following sciatic nerve injury(SNI) in rats. Transplantation of hDPSCs, STRO-1+ hDPSCs, or CD146+ hDPSCs after sciatic nerve transection inrats upregulated the levels of β3 tubulin, a marker of immature newborn neurons. Furthermore, the levels of glial cellderived neurotrophic factor, insulin-like growth factor 2, and the neuroregenerative factor NeuroD1 were upregulated. Motor dysfunction in rats with SNI was restored, as demonstrated by significantly higher sciatic functional indexscores compared with the sciatic nerve transection group without transplantation. Transplantation of hDPSCs intoinjured peripheral nerves results in the upregulation of neurotrophic factors, differentiation into immature neurons, andpromotion of motor function recovery. This approach holds promise as a valuable therapeutic strategy for repairinginjured peripheral sciatic nerves, potentially providing a solution for nerve damage in both the PNS and CNS.
Abstract
Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic resource for the peripheral nervoussystem (PNS) and central nervous system (CNS) that is attributable to their capacity for neuronal differentiation. Human dental pulp stem cells (hDPSCs), which exhibit MSC-like traits, can differentiate into neuron-like cellsand secrete critical neurotrophic factors; however, their therapeutic potential in peripheral nerve injury remainsunexplored. This study investigated the regenerative effects of hDPSC transplantation following sciatic nerve injury(SNI) in rats. Transplantation of hDPSCs, STRO-1+ hDPSCs, or CD146+ hDPSCs after sciatic nerve transection inrats upregulated the levels of β3 tubulin, a marker of immature newborn neurons. Furthermore, the levels of glial cellderived neurotrophic factor, insulin-like growth factor 2, and the neuroregenerative factor NeuroD1 were upregulated. Motor dysfunction in rats with SNI was restored, as demonstrated by significantly higher sciatic functional indexscores compared with the sciatic nerve transection group without transplantation. Transplantation of hDPSCs intoinjured peripheral nerves results in the upregulation of neurotrophic factors, differentiation into immature neurons, andpromotion of motor function recovery. This approach holds promise as a valuable therapeutic strategy for repairinginjured peripheral sciatic nerves, potentially providing a solution for nerve damage in both the PNS and CNS.
참고문헌 (38)
- Hall S, "Nerve repair : a neurobiologist’s view", J Hand Surg Br, 26, pp.129~136 (2001)[DOI]
- Nowacek A, "Neurodegenerative disorders and nanoformulated drug development", Nanomedicine(Lond), 4, pp.541~555 (2009)[DOI]
- Gupta AA, "Patterns of chemotherapy-induced toxicities in younger children and adolescents with rhabdomyosarcoma : a report from the Children’s Oncology Group Soft Tissue Sarcoma Committee", Cancer, 118, pp.1130~1137 (2012)[DOI]
- Zakrzewski W, "Stem cells : past, present, and future", Stem Cell Res Ther, 10, pp.68~ (2019)[DOI]
- Yamanaka S, "Pluripotent stem cell-based cell therapy-promise and challenges", Cell Stem Cell, 27, pp.523~531 (2020)[DOI]
- Wichterle H, "What can pluripotent stem cells teach us about neurodegenerative diseases?", Nat Neurosci, 13, pp.800~804 (2010)[DOI]
- Ross CA, "Human-induced pluripotent stem cells : potential for neurodegenerative diseases", Hum Mol Genet, 23(R1), pp.R17~26 (2014)[DOI]
- Olanow CW, "A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease", Ann Neurol, 54, pp.403~414 (2003)[DOI]
- Woloszyk A, "Human dental pulp stem cells and gingival fibroblasts seeded into silk fibroin scaffolds have the same ability in attracting vessels", Front Physiol, 7, pp.140~ (2016)[DOI]
- Tatullo M, "Dental pulp stem cells : function, isolation and applications in regenerative medicine", J Tissue Eng Regen Med, 9, pp.1205~1216 (2015)[DOI]
- Carnevale G, "Human dental pulp stem cells expressing STRO-1, c-kit and CD34 markers in peripheral nerve regeneration", J Tissue Eng Regen Med, 12, pp.e774~85 (2018)[DOI]
- Fernandez-Pernas P, "CD105+-mesenchymal stem cells migrate into osteoarthritis joint : an animal model", PLoS One, 12, pp.e0188072~ (2017)[DOI]
- Matsui M, "CD146 positive human dental pulp stem cells promote regeneration of dentin", pulplike structures, 2018, pp.31, 127~138
- Leong WK, "Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms", Stem Cells Transl Med, 1, pp.177~187 (2012)[DOI]
- Koutsoudaki PN, "Neural stem", progenitor cells differentiate into oligodendrocytes, reduce inflammation, and ameliorate learning deficits after transplantation in a mouse model of traumatic brain injury, 2016, pp.64, 763~779
- Sasaki R, "PLGA artificial nerve conduits with dental pulp cells promote facial nerve regeneration", J Tissue Eng Regen Med, 5, pp.823~830 (2011)[DOI]
- Ullah I, "Transplantation of human dental pulpderived stem cells or differentiated neuronal cells from human dental pulp-derived stem cells identically enhances regeneration of the injured peripheral nerve", Stem Cells Dev, 26, pp.1247~1257 (2017)[DOI]
- Ip CW, "Tor1a+", -mice develop dystonia-like movements via a striatal dopaminergic dysregulation triggered by peripheral nerve injury, 2016, pp.4, 108~
- Marconi S, "Human adipose-derived mesenchymal stem cells systemically injected promote peripheral nerve regeneration in the mouse model of sciatic crush", Tissue Eng Part A, 18, pp.1264~1272 (2012)[DOI]
- Allodi I, "Schwann cells transduced with a lentiviral vector encoding Fgf-2 promote motor neuron regeneration following sciatic nerve injury", Glia, 62, pp.1736~1746 (2014)[DOI]
- Sakai K, "Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuroregenerative mechanisms", J Clin Invest, 122, pp.80~90 (2012)[DOI]
- Xu L, "Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats", Mol Neurobiol, 46, pp.265~274 (2012)[DOI]
- Pettersson J, "Muscle recovery after repair of short and long peripheral nerve gaps using fibrin conduits", Neurosci Lett, 500, pp.41~46 (2011)[DOI]
- Xu J, "Multiple differentiation capacity of STRO-1+", CD146+ PDL mesenchymal progenitor cells, 2009, pp.18, 487~496
- Yan Q, "Use new PLGL-RGD-NGF nerve conduits for promoting peripheral nerve regeneration", Biomed Eng Online, 11, pp.36~ (2012)[DOI]
- Xie H, "A silk sericin", silicone nerve guidance conduit promotes regeneration of a transected sciatic nerve, 2015, pp.4, 2195~2205
- Coumans JV, "Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins", J Neurosci, 21, pp.9334~9344 (2001)[DOI]
- Perets N, "Long term beneficial effect of neurotrophic factors-secreting mesenchymal stem cells transplantation in the BTBR mouse model of autism", Behav Brain Res, 331, pp.254~260 (2017)[DOI]
- Ziegler AN, "Insulin-like growth factor II : an essential adult stem cell niche constituent in brain and intestine", Stem Cell Reports, 12, pp.816~830 (2019)[DOI]
- Gao X, "GDNF enhances therapeutic efficiency of neural stem cells-based therapy in chronic experimental allergic encephalomyelitis in rat", Stem Cells Int, 2016, pp.1431349~ (2016)[DOI]
- Lai M, "NeuroD1 overexpression in spinal neurons accelerates axonal regeneration after sciatic nerve injury", Exp Neurol, 327, pp.113215~ (2020)[DOI]
- Hwang K, "Glial cell line-derived neurotrophic factor-overexpressing human neural stem", progenitor cells enhance therapeutic efficiency in rat with traumatic spinal cord injury, 2019, pp.28, 679~696
- Martín-Montañez E, "IGF-II promotes neuroprotection and neuroplasticity recovery in a long-lasting model of oxidative damage induced by glucocorticoids", Redox Biol, 13, pp.69~81 (2017)[DOI]
- Fitzgerald GS, "Insulin-like growth factor-2 is a promising candidate for the treatment and prevention of Alzheimer’s disease", CNS Neurosci Ther, 29, pp.1449~1469 (2023)[DOI]
- Molnár K, "Motoneuronal inflammasome activation triggers excessive neuroinflammation and impedes regeneration after sciatic nerve injury", J Neuroinflammation, 19, pp.68~ (2022)[DOI]
- Bingham JR, ""Stem cell therapy to promote limb function recovery in peripheral nerve damage in a rat model"-Experimental research", Ann Med Surg(Lond), 41, pp.20~28 (2019)[DOI]
- Trounson A, "Stem cell therapies in clinical trials : progress and challenges", Cell Stem Cell, 17, pp.11~22 (2015)[DOI]
- Singh AK, "Allogeneic stem cell transplantation : a historical and scientific overview", Cancer Res, 76, pp.6445~6451 (2016)[DOI]