Priming with FGF2 stimulates human dental pulp cells to promote axonal regeneration and locomotor function recovery after spinal cord injury

Nagashima, Kosuke; Miwa, Takahiro; Soumiya, Hitomi; Ushiro, Daisuke; Takeda-Kawaguchi, Tomoko; Tamaoki, Naritaka; Ishiguro, Saho; Sato, Yumi; Miyamoto, Kei; Ohno, Takatoshi; Osawa, Masatake; Kunisada, Takahiro; Shibata, Toshiyuki; Tezuka, Ken Ichi; Furukawa, Shoei; Fukumitsu, Hidefumi

doi:10.1038/s41598-017-13373-5

Cited by 21 publications

(18 citation statements)

References 34 publications

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“…Some axonal regeneration and locomotor recovery were observed. 198 In vitro, astrocytes were transfected to overexpress nerve growth factor (NGF) and encapsulated into a collagen scaffold. They were then added to rat dorsal root ganglion culture and found to significantly enhance axonal growth.…”

Section: Reproduced Withmentioning

confidence: 99%

Regenerative Therapies for Spinal Cord Injury

Ashammakhi

Kim

Ehsanipour

et al. 2019

Tissue Engineering Part B: Reviews

116

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Spinal cord injury (SCI) is a serious problem that primarily affects younger and middle-aged adults at its onset. To date, no effective regenerative treatment has been developed. Over the last decade, researchers have made significant advances in stem cell technology, biomaterials, nanotechnology, and immune engineering, which may be applied as regenerative therapies for the spinal cord. Although the results of clinical trials using specific cell-based therapies have proven safe, their efficacy has not yet been demonstrated. The pathophysiology of SCI is multifaceted, complex and yet to be fully understood. Thus, combinatorial therapies that simultaneously leverage multiple approaches will likely be required to achieve satisfactory outcomes. Although combinations of biomaterials with pharmacologic agents or cells have been explored, few studies have combined these modalities in a systematic way. For most strategies, clinical translation will be facilitated by the use of minimally invasive therapies, which are the focus of this review. In addition, this review discusses previously explored therapies designed to promote neuroregeneration and neuroprotection after SCI, while highlighting present challenges and future directions.

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Section: Reproduced Withmentioning

confidence: 99%

Regenerative Therapies for Spinal Cord Injury

Ashammakhi

Kim

Ehsanipour

et al. 2019

Tissue Engineering Part B: Reviews

116

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“…Additionally, a recent study showed that injection of DPCs into rat spinal cord injury significantly improved axon regeneration and functional recovery, and this effect was further enhanced when the DPCs were cultured with fibroblast growth factor 2 (FGF2). 31 Therefore, engineering a method to deliver DPCs to a site of PNI could be an effective means of sustained NTF delivery, and priming DPCs with FGF2 may enhance the bioactivity of these cells for use in regenerative peripheral nerve therapies.…”

Section: Introductionmentioning

confidence: 99%

Dental Pulp Cell Sheets Enhance Facial Nerve Regeneration via Local Neurotrophic Factor Delivery

Ahmed

Shi

Dailey

et al. 2021

Tissue Engineering Part A

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An effective strategy for sustained neurotrophic factor (NTF) delivery to sites of peripheral nerve injury (PNI) would accelerate healing and enhance functional recovery, addressing the major clinical challenges associated with the current standard of care. In this study, scaffold-free cell sheets were generated using human dental pulp stem/progenitor cells, that endogenously express high levels of NTFs, for use as bioactive NTF delivery systems. Additionally, the effect of fibroblast growth factor 2 (FGF2) on NTF expression by dental pulp cell (DPC) sheets was evaluated. In vitro analysis confirmed that DPC sheets express high levels of NTF messenger RNA (mRNA) and proteins, and the addition of FGF2 to DPC sheet culture increased total NTF production by significantly increasing the cellularity of sheets. Furthermore, the DPC sheet secretome stimulated neurite formation and extension in cultured neuronal cells, and these functional effects were further enhanced when DPC sheets were cultured with FGF2. These neuritogenic results were reversed by NTF inhibition substantiating that DPC sheets have a positive effect on neuronal cell activity through the production of NTFs. Further evaluation of DPC sheets in a rat facial nerve crush injury model in vivo established that in comparison with untreated controls, nerves treated with DPC sheets had greater axon regeneration through the injury site and superior functional recovery as quantitatively assessed by compound muscle action potential measurements. This study demonstrates the use of DPC sheets as vehicles for NTF delivery that could augment the current methods for treating PNIs to accelerate regeneration and enhance the functional outcome.

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“…7 The microenvironment of the spinal cord changes immediately after a mechanical crushing or stretching of the spinal cord. [8][9][10] Axonal damage and cell membrane disruption cause glia loss in the primary injury of the spinal cord. 11 Then, a cascade of molecular and signaling pathways initiate a series of secondary injuries to the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Polycaprolactone electrospun fiber scaffold loaded with iPSCs-NSCs and ASCs as a novel tissue engineering scaffold for the treatment of spinal cord injury

Zhou¹,

Shi²,

Fan³

et al. 2018

IJN

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BackgroundSpinal cord injury (SCI) is a traumatic disease of the central nervous system, accompanied with high incidence and high disability rate. Tissue engineering scaffold can be used as therapeutic systems to provide effective repair for SCI.PurposeIn this study, a novel tissue engineering scaffold has been synthesized in order to explore the effect of nerve repair on SCI.Patients and methodsPolycaprolactone (PCL) scaffolds loaded with actived Schwann cells (ASCs) and induced pluripotent stem cells -derived neural stem cells (iPSC-NSCs), a combined cell transplantation strategy, were prepared and characterized. The cell-loaded PCL scaffolds were further utilized for the treatment of SCI in vivo. Histological observation, behavioral evaluation, Western-blot and qRT-PCR were used to investigate the nerve repair of Wistar rats after scaffold transplantation.ResultsThe iPSCs displayed similar characteristics to embryonic stem cells and were efficiently differentiated into neural stem cells in vitro. The obtained PCL scaffolds werê0.5 mm in thickness with biocompatibility and biodegradability. SEM results indicated that the ASCs and (or) iPS-NSCs grew well on PCL scaffolds. Moreover, transplantation reduced the volume of lesion cavity and improved locomotor recovery of rats. In addition, the degree of spinal cord recovery and remodeling maybe closely related to nerve growth factor and glial cell-derived neurotrophic factor. In summary, our results demonstrated that tissue engineering scaffold treatment could increase tissue remodeling and could promote motor function recovery in a transection SCI model.ConclusionThis study provides preliminary evidence for using tissue engineering scaffold as a clinically viable treatment for SCI in the future.

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Priming with FGF2 stimulates human dental pulp cells to promote axonal regeneration and locomotor function recovery after spinal cord injury

Cited by 21 publications

References 34 publications

Regenerative Therapies for Spinal Cord Injury

Regenerative Therapies for Spinal Cord Injury

Dental Pulp Cell Sheets Enhance Facial Nerve Regeneration via Local Neurotrophic Factor Delivery

Polycaprolactone electrospun fiber scaffold loaded with iPSCs-NSCs and ASCs as a novel tissue engineering scaffold for the treatment of spinal cord injury

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