Towards clinical translation of ‘second-generation’ regenerative stroke therapies: hydrogels as game changers?

Totten, John D.; Alhadrami, Hani A.; Jiffri, Essam H.; McMullen, C. H.; Seib, F. Philipp; Carswell, Hilary V O

doi:10.1016/j.tibtech.2021.10.009

Cited by 14 publications

(4 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In chronic cerebral stroke, glial scar tissues form around the cavity and the cortex often collapses. [ 39 ] In the mice that received transplantation without the cocktail, the cortex collapsed and few or no GFP+ cells were present at 30 days after transplantation ( Figure ). Strong glial reaction was present in and surrounding the ischemic site, as evidenced by strong staining for a microglial marker Iba1 and an astrocyte marker GFAP (Figure 3a,b).…”

Section: Resultsmentioning

confidence: 99%

Enabling Survival of Transplanted Neural Precursor Cells in the Ischemic Brain

Wang,

Zheng,

Tan

et al. 2023

Advanced Science

View full text Add to dashboard Cite

There is no effective therapy for ischemic stroke following the acute stage. Neural transplantation offers a potential option for repairing the ischemic lesion. However, this strategy is hindered by the poor survival of the neural precursor cells (NPCs) that are transplanted into the inflammatory ischemic core. Here, a chemical cocktail consisting of fibrinogen and maraviroc is developed to promote the survival of the transplanted NPCs in the ischemic core of the mouse cerebral cortex. The grafted NPCs survive in the presence of the cocktail but not fibrinogen or maraviroc alone at day 7. The surviving NPCs divide and differentiate to mature neurons by day 30, reconstituting the infarct cortex with vascularization. Molecular analysis in vivo and in vitro shows that blocking the activation of CCR5 on the NPCs protects the NPCs from apoptosis induced by pro‐inflammatory factors, revealing the underlying protective effect of the cocktail for NPCs. The findings open an avenue to enable survival of the transplanted NPCs under the inflammatory neurological conditions like stroke.

show abstract

Section: Resultsmentioning

confidence: 99%

Enabling Survival of Transplanted Neural Precursor Cells in the Ischemic Brain

Wang,

Zheng,

Tan

et al. 2023

Advanced Science

View full text Add to dashboard Cite

show abstract

“…Alginates were previously considered scaffolds or drug delivery systems for nerve tissue engineering [ 15 , 16 , 17 , 18 ]. Moreover, alginate hydrogels were shown to enhance the survival of transplanted cells and improve outcomes in animal models of cardiac infarction [ 19 ], hind limb ischemia [ 20 ], and spinal cord injury [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Manganese-Labeled Alginate Hydrogels for Image-Guided Cell Transplantation

Araszkiewicz

Oliveira

Svendsen

et al. 2022

IJMS

View full text Add to dashboard Cite

Cell transplantation has been studied extensively as a therapeutic strategy for neurological disorders. However, to date, its effectiveness remains unsatisfactory due to low precision and efficacy of cell delivery; poor survival of transplanted cells; and inadequate monitoring of their fate in vivo. Fortunately, different bio-scaffolds have been proposed as cell carriers to improve the accuracy of cell delivery, survival, differentiation, and controlled release of embedded stem cells. The goal of our study was to establish hydrogel scaffolds suitable for stem cell delivery that also allow non-invasive magnetic resonance imaging (MRI). We focused on alginate-based hydrogels due to their natural origin, biocompatibility, resemblance to the extracellular matrix, and easy manipulation of gelation processes. We optimized the properties of alginate-based hydrogels, turning them into suitable carriers for transplanted cells. Human adipose-derived stem cells embedded in these hydrogels survived for at least 14 days in vitro. Alginate-based hydrogels were also modified successfully to allow their injectability via a needle. Finally, supplementing alginate hydrogels with Mn ions or Mn nanoparticles allowed for their visualization in vivo using manganese-enhanced MRI. We demonstrated that modified alginate-based hydrogels can support therapeutic cells as MRI-detectable matrices.

show abstract

“…To date, efforts at promoting regeneration in the brain after stroke have achieved limited success. Hydrogels have garnered interest in this arena because of their ability to provide a scaffold for the delivery of potential regenerative therapeutics such as stem cells . However, a significant gap persists in identifying functional materials for modifying innate neuroplasticity.…”

Section: Introductionmentioning

confidence: 99%

“…Hydrogels have garnered interest in this arena because of their ability to provide a scaffold for the delivery of potential regenerative therapeutics such as stem cells. 20 However, a significant gap persists in identifying functional materials for modifying innate neuroplasticity. Electrical stimulation can influence cell proliferation, differentiation, migration, and integration, 21 and experimental studies with noninvasive transcranial direct current stimulation show promise for improving functional recovery after stroke.…”

Section: ■ Introductionmentioning

confidence: 99%

In Vivo Formation and Tracking of π-Peptide Nanostructures

Dibble

DeBoer

Mersha³

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

The photophysics associated with the self-assembly of π-peptide molecules into 1-D nanostructures has been wellestablished, thus revealing the creation of nanoscale electronic conduits in aqueous media. Such materials have therapeutic potential in many biomedical applications. In this work, we report the in vivo deployment of these π-peptide nanostructures in brain tissue using photothrombotic stroke as a model application. A test peptide was used for brain injections, and the nanostructures formed were visualized with electron microscopy. A new peptide bearing a low-energy fluorescence dye was prepared to facilitate direct visualization of π-peptide localization in the brain cavity by way of fluorescence microscopy. This work demonstrates feasibility for in vivo application of π-peptide nanostructures toward pressing biomedical challenges.

show abstract

Towards clinical translation of ‘second-generation’ regenerative stroke therapies: hydrogels as game changers?

Cited by 14 publications

References 96 publications

Enabling Survival of Transplanted Neural Precursor Cells in the Ischemic Brain

Enabling Survival of Transplanted Neural Precursor Cells in the Ischemic Brain

Manganese-Labeled Alginate Hydrogels for Image-Guided Cell Transplantation

In Vivo Formation and Tracking of π-Peptide Nanostructures

Contact Info

Product

Resources

About