Engineered hydrogels increase the post-transplantation survival of encapsulated hESC-derived midbrain dopaminergic neurons

Adil, Maroof M.; Vazin, Tandis; Ananthanarayanan, Badriprasad; Rodrigues, Gonçalo; Rao, Antara T.; Kulkarni, Rishikesh U.; Miller, Evan W.; Kumar, Sanjay; Schaffer, David V.

doi:10.1016/j.biomaterials.2017.05.008

Cited by 101 publications

(110 citation statements)

References 71 publications

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“…On injection, the fluid flows to fill extracellular spaces in the brain, filling irregular voids (where required) and interfacing fully with surrounding tissue, then promptly selfassembling within minutes into a stiffer gel that can be tailored to match the mechnical properties of the brain, and support surrounding host, or newly implanted cells. Such materials [including hyaluronic acid (HA) and collagen gels] have been shown to support both fetal and human PSC-derived progenitors in vitro and cell engraftment in PD and stroke models (Jin et al, 2010;Yu et al, 2010;Zhong et al, 2010;Adil et al, 2017;Moriarty et al, 2017Moriarty et al, , 2018a; see also reviews -Jendelova et al, 2016; Moriarty and Dowd, 2018c;Moriarty et al, 2018b).…”

Section: Figurementioning

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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Section: Figurementioning

confidence: 99%

Harnessing stem cells and biomaterials to promote neural repair

Bruggeman

Moriarty

Dowd

et al. 2018

British J Pharmacology

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“…Second, Adil et al. () showed that a heparin/RGD‐functionalised hyaluronic acid hydrogel could improve the survival of transplanted human embryonic stem cell‐derived dopaminergic neurons. Finally, Moriarty et al.…”

Section: Cellular Brain Repair For Parkinson's Disease – Potential Ofmentioning

confidence: 99%

“…First, in the study by Wang et al (2016), a GDNF-functionalised composite poly(l-lactic acid)/xyloglucan hydrogel, where GDNF was blended into and/or covalently attached to the scaffold, was shown to enhance survival of, and striatal reinnervation from, transplanted mouse VM grafts in parkinsonian mice. Second, Adil et al (2017) showed that a heparin/RGD-functionalised hyaluronic acid hydrogel could improve the survival of transplanted human embryonic stem cell-derived dopaminergic neurons. Finally, Moriarty et al (2017 demonstrated that encapsulating VM grafts in a GDNF-loaded collagen hydrogel resulted in a dramatic increase in the survival of dopaminergic neurons and that this correlated with enhanced striatal reinnervation and restoration of motor function in hemiparkinsonian rats.…”

Section: F I G U R E 1 Therapeutic Concept Of Biomaterials For Brain mentioning

confidence: 99%

Primary tissue for cellular brain repair in Parkinson's disease: Promise, problems and the potential of biomaterials

Moriarty

Parish

Dowd

2018

Eur J of Neuroscience

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The dopamine precursor, levodopa, remains the "gold standard" treatment for Parkinson's disease, and, although it provides superlative efficacy in the early stages of the disease, its long-term use is limited by the development of severe motor side effects and a significant abating of therapeutic efficacy. Therefore, there remains a major unmet clinical need for the development of effective neuroprotective, neurorestorative or neuroreparatory therapies for this condition. The relatively selective loss of dopaminergic neurons from the nigrostriatal pathway makes Parkinson's disease an ideal candidate for reparative cell therapies, wherein the dopaminergic neurons that are lost in the condition are replaced through direct cell transplantation into the brain. To date, this approach has been developed, validated and clinically assessed using dopamine neuron-rich foetal ventral mesencephalon grafts which have been shown to survive and reinnervate the denervated brain after transplantation, and to restore motor function. However, despite long-term symptomatic relief in some patients, significant limitations, including poor graft survival and the impact this has on the number of foetal donors required, have prevented this therapy being more widely adopted as a restorative approach for Parkinson's disease. Injectable biomaterial scaffolds have the potential to improve the delivery, engraftment and survival of these grafts in the brain through provision of a supportive microenvironment for cell adhesion, growth and immune shielding. This article will briefly review the development of primary cell therapies for brain repair in Parkinson's disease and will consider the emerging literature which highlights the potential of using injectable biomaterial hydrogels in this context.

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“…We have recently reported that a rationally-designed 3D HA scaffold could support the maturation and implantation of fragile midbrain dopaminergic (mDA) neurons differentiated from hESCs [75]. The HA scaffold offered distinct advantages over culturing cells in 2D or injecting a dissociated cell suspension, including brain-mimetic mechanical tuning (350 Pa), conjugation of chemical factors that promote cellular adhesion and neurite extension (RGD and heparin), and physical protection during injection.…”

Section: Engineered Materials For Improved Neural Tissue Engineeringmentioning

confidence: 99%

Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

Kang

Kumar

Schaffer

2017

Current Opinion in Biomedical Engineering

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Neural stem cells (NSCs) are a valuable cell source for tissue engineering, regenerative medicine, disease modeling, and drug screening applications. Analogous to other stem cells, NSCs are tightly regulated by their microenvironmental niche, and prior work utilizing NSCs as a model system with engineered biomaterials has offered valuable insights into how biophysical inputs can regulate stem cell proliferation, differentiation, and maturation. In this review, we highlight recent exciting studies with innovative material platforms that enable narrow stiffness gradients, mechanical stretching, temporal stiffness switching, and three-dimensional culture to study NSCs. These studies have significantly advanced our knowledge of how stem cells respond to an array of different biophysical inputs and the underlying mechanosensitive mechanisms. In addition, we discuss efforts to utilize engineered material scaffolds to improve NSC-based translational efforts and the importance of mechanobiology in tissue engineering applications.

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Engineered hydrogels increase the post-transplantation survival of encapsulated hESC-derived midbrain dopaminergic neurons

Cited by 101 publications

References 71 publications

Harnessing stem cells and biomaterials to promote neural repair

Harnessing stem cells and biomaterials to promote neural repair

Primary tissue for cellular brain repair in Parkinson's disease: Promise, problems and the potential of biomaterials

Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

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