Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair

Uemura, Takuya; Takamatsu, Kiyohito; Ikeda, Mikinori; Okada, Mitsuhiro; Kazuki, Kenichi; Ikada, Yoshito; Nakamura, Hiroaki

doi:10.1016/j.bbrc.2012.01.154

Cited by 71 publications

(67 citation statements)

References 29 publications

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“…In addition to differentiation into various somatic cell lines, established protocols now exist for the in vitro differentiation of iPSCs along neural lineages [143,144] . Although evidence suggests that differentiation occurs with reduced efficiency and increased variability [145] , iPSCs have been shown to have a pro-regenerative effect in small animal models of central and peripheral nervous system injury [146][147][148][149] . These cells possess several advantages over embryonic sources such as the avoidance of ethical and immunosuppressive issues.…”

Section: Skin Derived Precursorsmentioning

confidence: 99%

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

Fairbairn

Meppelink

Ng-Glazier

et al. 2015

WJSC

124

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Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell (SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration.

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Section: Skin Derived Precursorsmentioning

confidence: 99%

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

Fairbairn

Meppelink

Ng-Glazier

et al. 2015

WJSC

124

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“…1 a) as described previously [Uemura et al, 2011[Uemura et al, , 2012Ikeda et al, 2014]. The lumen wall of the tube was bilayered.…”

Section: Preparation Of Nerve Conduits Coated With Ipsc-derived Neuromentioning

confidence: 99%

“…Here, we examine the utility of iPScs in regenerative therapy of peripheral nerves with nerve conduits, and for the first time develop nerve conduits coated with iPSc-derived neurospheres [Uemura et al, 2011]. Our previous report on the transplantation of iPSc-derived neurospheres with nerve conduits demonstrated enhanced axon regeneration in the 12 weeks following their implantation in mice [Uemura et al, 2012]. Logically, the long-term outcomes of this treatment now require investigation.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Efficacy and Safety Outcomes of Transplantation of Induced Pluripotent Stem Cell-Derived Neurospheres with Bioabsorbable Nerve Conduits for Peripheral Nerve Regeneration in Mice

Uemura

Ikeda

Takamatsu

et al. 2014

Cells Tissues Organs

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The induced pluripotent stem cell (iPSc) offers great potential for cell-based therapy in regenerative medicine. We previously developed tissue-engineered bioabsorbable nerve conduits coated with iPSc-derived neurospheres for use in peripheral nerve repair. Here, we examine the long-term efficacy and safety of using nerve conduits with iPSc technology for peripheral nerve repair in mice. The nerve conduit consisted of an outer layer of a poly L-lactide mesh and an inner layer of porous sponge composed of 50% L-lactide and 50% ε-caprolactone. Secondary neurospheres were derived from mouse iPScs, resuspended and cultured within the conduit for 14 days. Conduits were implanted within surgically administered 5-mm defects in the left sciatic nerve of mice (iPSc group; n = 14). The defects in the control group (n = 13) were reconstructed using the nerve conduit alone. At 4, 8, 12, 24 and 48 weeks postsurgery, motor and sensory functional recovery in the iPSc group had improved significantly more than in the control group. At 24 and 48 weeks, histological analysis revealed axonal regeneration in the nerve conduits of both groups. However, axonal regeneration and myelination were significantly enhanced in the iPSc group. No teratomas were identified in the iPSc group at any time point. Therefore, we here demonstrate that bioabsorbable nerve conduits coated with iPSc-derived neurospheres promote enhanced regeneration of peripheral nerves and functional recovery without teratoma formation in the long term. This combination of iPSc technology and bioabsorbable nerve conduits has the potential to be a safe future tool for the treatment of peripheral nerve defects.

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“…Theoretically, with the transplantation of specific cells created from autologus iPS cells, the cells that lacking can be replenished and replace by cells with the defects corrected, thereby relieving a patient`s symptoms. The mostly use somatic cells are fibroblasts, but different groups generated also iPS cells from other somatic cells providing evidence that is possible to reprogram cells of different origins (Deng, 2010;Ebben et al, 2011;Patel and Yang, 2010;Uemura et al, 2012;Vitale et al, 2011;Walia et al, 2012;Wong and Chiu, 2011;Zeng and Zhou, 2011). Other sources of iPSCs that can be easily reprogrammed are human keratinocytes (Aasent et al, 2008;Petit et al, 2012), oral mucosa fibroblasts (Miyoshi et al, 2010), dermal papilla cells (Tsai et al, 2010), pancreatic beta cells (Stadtfeld et al, 2008), neural stem cells (Kim et al, 2009), mature B lymphocytes (Hanna et al, 2008), liver and stomach cells (Aoi et al, 2008) and cord blood cells (Cai et al, 2010;Takenaka et al, 2009).…”

Section: Applications Of Human Ipscsmentioning

confidence: 99%

Induced Pluripotent Stem Cells and Their Implication for Biomedical Sciences

Csobonyeiová¹

2013

OnLine Journal of Biological Sciences

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The groundbreaking discovery, that somatic mammalian cells can be epigenetically reprogrammed to a pluripotent state through the exogenous expression of the transcription factors Oct4, Sox2, Klf4 and c-myc, has yielded a new cell type for potential application in regenerative medicine, the induced Pluripotent Stem Cells (iPSCs). Since the first demonstration of creating iPSCs in 2006 great efforts have been made into improving iPS cell generation methods and understanding the reprogramming mechanism as well as the nature of iPSCs. The iPSCs technique makes it possible to produce patient-specific pluripotent stem cells for transplantation therapy without immune rejection. However, some restriction still remain, including viral vector integration into the genome, the existence of exogenous oncogenic factors and low induction efficiency. In this review we discuss recent advances in methods of generating safer iPSCs lines and their possible use for biomedical applications.

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Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair

Cited by 71 publications

References 29 publications

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

Long-Term Efficacy and Safety Outcomes of Transplantation of Induced Pluripotent Stem Cell-Derived Neurospheres with Bioabsorbable Nerve Conduits for Peripheral Nerve Regeneration in Mice

Induced Pluripotent Stem Cells and Their Implication for Biomedical Sciences

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