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Review
. 2018 May;49(5):1099-1106.
doi: 10.1161/STROKEAHA.117.018293. Epub 2018 Apr 18.

Future of Animal Modeling for Poststroke Tissue Repair

Michel M Modo  1 , Jukka Jolkkonen  2   3 , Marietta Zille  4   5 , Johannes Boltze  6
Affiliations
Review

Future of Animal Modeling for Poststroke Tissue Repair

Michel M Modo et al. Stroke. 2018 May.
No abstract available

Keywords: graft survival; immunomodulation; neurogenesis; regeneration; stem cell transplantation.

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Figures

Figure 1
Figure 1. Application of biomaterials in repairing stroke brain
(A) Biomaterials enable local release of factors and/or provide structural support in case of tissue loss. The least invasive means to deliver factors to the stroke damage brain is by the epi-cortical placement of biomaterials, such as hydrogel, releasing factors into the surrounding cortex (I.). Hydrogels can also serve as a scaffolding material in the lesion cavity (II.). An injection-drainage approach is preferable to ensure homogenous filling of the volume. Repair response in the peri-infarct area can be influenced by injecting microparticles that release growth factors, and that would not easily penetrate across the blood-brain barrier (III.). Injection of microparticles into the lateral ventricle (IV.) can be used to influence the sub-ependymal zone to increase neurogenesis. (B) Exemplary overview immunofluorescent staining of brain slice showing ECM hydrogel (detected by collagen I in green) in the lesion cavity.
Figure 2
Figure 2. Research strategy draft for clinical translation of tissue restoration in stroke
After identification of the target patient population, a stroke model well reflecting this population is selected. The tissue restoration strategy, ideally combined with a supportive strategy, is then applied to this model in a basic (exploratory) efficacy trial. In the second step, the typical comorbidity and confounder profile of the target patient population is simulated in the stroke model for an advanced (confirmative) efficacy test, which should also include a thorough safety endpoint. If required, large animal modeling can be used for advanced safety assessments or therapy optimization before moving on to clinical investigations.
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References

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