Harnessing the Potential of Biomaterials for Brain Repair after Stroke

Tuladhar, Anup; Payne, Samantha L.; Shoichet, Molly S.

doi:10.3389/fmats.2018.00014

Cited by 36 publications

(41 citation statements)

References 290 publications

(352 reference statements)

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“…(1) artificial cerebrospinal fluid (aCSF), a buffer to mimic circulating CSF, and (2) a hyaluronan methylcellulose hydrogel (HAMC), which has been shown to improve xenograft survival in the CNS [17,22]. To determine the effect of vehicle on the number of live cells at the time of transplantation, we performed a live/dead assay on cells prior to and following injection through the syringe.…”

Section: Cell Viability Is Not Dependent On the Transplant Vehiclementioning

confidence: 99%

“…With clinical translation in mind, we examined the therapeutic potential of a population of human cells that have been directly reprogrammed from somatic cells to NPCs, without passing through a pluripotent state during reprogramming. We address important considerations that may influence transplant success, including the transplant vehicle [22], and the sex of the stroke-injured mice, which has not been adequately studied to date despite the observation that males and females are differentially responsive to stroke injury [12,[23][24][25][26]. Furthermore, we explore the importance of cell survival for recovery and investigate changes in synaptogenesis as a mechanism underlying cell-mediated effects.…”

Section: Introductionmentioning

confidence: 99%

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Transplantation of Directly Reprogrammed Human Neural Precursor Cells Following Stroke Promotes Synaptogenesis and Functional Recovery

Vonderwalde

Azimi

Rolvink

et al. 2019

Transl. Stroke Res.

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Stroke is one of the leading causes of long-term disability. Cell transplantation is a promising strategy to treat stroke. We explored the efficacy of directly reprogrammed human neural precursor cell (drNPC) transplants to promote functional recovery in a model of focal ischemic stroke in the mouse sensorimotor cortex. We show that drNPCs express neural precursor cell markers and are neurally committed at the time of transplantation. Mice that received drNPC transplants recovered motor function, irrespective of transplant vehicle or recipient sex, and with no correlation to lesion volume or glial scarring. The majority of drNPCs found in vivo, at the time of functional recovery, remained undifferentiated. Notably, no correlation between functional recovery and long-term xenograft survival was observed, indicating that drNPCs provide therapeutic benefits beyond their survival. Furthermore, increased synaptophysin expression in transplanted brains suggests that drNPCs promote neuroplasticity through enhanced synaptogenesis. Our findings provide insight into the mechanistic underpinnings of drNPC-mediated recovery for stroke and support the notion that drNPCs may have clinical applications for stroke therapy.

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Section: Cell Viability Is Not Dependent On the Transplant Vehiclementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transplantation of Directly Reprogrammed Human Neural Precursor Cells Following Stroke Promotes Synaptogenesis and Functional Recovery

Vonderwalde

Azimi

Rolvink

et al. 2019

Transl. Stroke Res.

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“…As demonstrated by Zhang and colleagues, the effect of scaffold implantation on the integrity of brain shape can be simply shown by haematoxylin and eosin staining of rat brain sections or by extracting and visually observing the whole brain ( 71 ). Regenerative medicine therapies may increase post-stroke neurogenesis ( 72 ), which can be assessed by doublecortin and NeuN/BrdU immunohistochemistry ( 73 ). Induction of post-stroke angiogenesis is considered to be beneficial and can be imaged by laminin immunohistochemistry ( 44 ).…”

Section: Anti-inflammatory Strategies In Regenerative Medicinementioning

confidence: 99%

Regenerative Medicine Therapies for Targeting Neuroinflammation After Stroke

2018

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Inflammation is a major pathological event following ischemic stroke that contributes to secondary brain tissue damage leading to poor functional recovery. Following the initial ischemic insult, post-stroke inflammatory damage is driven by initiation of a central and peripheral innate immune response and disruption of the blood-brain barrier (BBB), both of which are triggered by the release of pro-inflammatory cytokines and infiltration of circulating immune cells. Stroke therapies are limited to early cerebral blood flow reperfusion, and whilst current strategies aim at targeting neurodegeneration and/or neuroinflammation, innovative research in the field of regenerative medicine aims at developing effective treatments that target both the acute and chronic phase of inflammation. Anti-inflammatory regenerative strategies include the use of nanoparticles and hydrogels, proposed as therapeutic agents and as a delivery vehicle for encapsulated therapeutic biological factors, anti-inflammatory drugs, stem cells, and gene therapies. Biomaterial strategies—through nanoparticles and hydrogels—enable the administration of treatments that can more effectively cross the BBB when injected systemically, can be injected directly into the brain, and can be 3D-bioprinted to create bespoke implants within the site of ischemic injury. In this review, these emerging regenerative and anti-inflammatory approaches will be discussed in relation to ischemic stroke, with a perspective on the future of stroke therapies.

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“…In this context, a non-degradable scaffold that provides a bridging network for the support of axonal regeneration may be more optimal. The requirements for stroke are similarwhere decreasing the lesion volume can result in significant functional improvement through the support of both endogenous and grafted cells (Somaa et al, 2017;Nisbet et al, 2018;Tuladhar et al, 2018). In the context of more discrete injuries such as PD and Huntington's disease, a scaffold that provides physical and chemical support for the survival and differentiation of cells upon implantation, but then slowly degrades once the cells have appropriately integrated within the host circuitry, may be a desirable alternative.…”

Section: Scaffold Biodegradationmentioning

confidence: 99%

“…In the aforementioned stroke study, the relative concentrations of two growth factors were optimized before in vivo testing, but there was no attempt to independently control their release (Moshayedi et al, 2016). The prevelance of heparin binding among natural ECM proteins can also present complications in vivo, when host ECM proteins are abundant (Tuladhar et al, 2018). Consequently, newer stategies are being developed to provide more specific heparin binding, including the use of heparin fractions with protein-specific affinity (Wang et al, 2014a,b).…”

Section: Encapsulation Of Proteins Within Biomaterialsmentioning

confidence: 99%

Harnessing stem cells and biomaterials to promote neural repair

Bruggeman

Moriarty

Dowd

et al. 2018

British J Pharmacology

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With the limited capacity for self‐repair in the adult CNS, efforts to stimulate quiescent stem cell populations within discrete brain regions, as well as harness the potential of stem cell transplants, offer significant hope for neural repair. These new cells are capable of providing trophic cues to support residual host populations and/or replace those cells lost to the primary insult. However, issues with low‐level adult neurogenesis, cell survival, directed differentiation and inadequate reinnervation of host tissue have impeded the full potential of these therapeutic approaches and their clinical advancement. Biomaterials offer novel approaches to stimulate endogenous neurogenesis, as well as for the delivery and support of neural progenitor transplants, providing a tissue‐appropriate physical and trophic milieu for the newly integrating cells. In this review, we will discuss the various approaches by which bioengineered scaffolds may improve stem cell‐based therapies for repair of the CNS.

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Harnessing the Potential of Biomaterials for Brain Repair after Stroke

Cited by 36 publications

References 290 publications

Transplantation of Directly Reprogrammed Human Neural Precursor Cells Following Stroke Promotes Synaptogenesis and Functional Recovery

Transplantation of Directly Reprogrammed Human Neural Precursor Cells Following Stroke Promotes Synaptogenesis and Functional Recovery

Regenerative Medicine Therapies for Targeting Neuroinflammation After Stroke

Harnessing stem cells and biomaterials to promote neural repair

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