Nanoparticle encapsulated core-shell hydrogel for on-site BMSCs delivery protects from iron overload and enhances functional recovery

Gong, Yuhua; Wang, Yumei; Qu, Qing; Hou, Zongkun; Guo, Tingwang; Xu, Yingqian; Qing, Rui; Deng, Jia; Wang, Bochu; Hao, Shilei

doi:10.1016/j.jconrel.2020.01.029

Cited by 34 publications

(38 citation statements)

References 46 publications

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“…To improve the iron overload microenvironment after ICH, an injectable core-shell hydrogel was fabricated for ICH in situ therapy. The outer shell hydrogel with quick degradation property was loaded with iron chelator to eliminate iron overload, and the inner core hydrogel loaded with MSCs and growth factors displayed an improved MSCs survival and differentiation (Gong et al, 2020). In addition, surgical evacuation was a commonly used clinical approach to remove hematoma, and the benefits of combined treatment with MSCs transplantation might associate with the improvement of the transplanted cells microenvironment (Zhang Q. et al, 2015;Chang et al, 2016).…”

Section: Optimizing Ich Microenvironmentmentioning

confidence: 99%

Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges

Gong

Hao

Wang

2021

Front. Cell. Neurosci.

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Intracerebral hemorrhage (ICH) is one of the leading causes of death and long-term disability worldwide. Mesenchymal stem cell (MSC) therapies have demonstrated improved outcomes for treating ICH-induced neuronal defects, and the neural network reconstruction and neurological function recovery were enhanced in rodent ICH models through the mechanisms of neurogenesis, angiogenesis, anti-inflammation, and anti-apoptosis. However, many key issues associated with the survival, differentiation, and safety of grafted MSCs after ICH remain to be resolved, which hinder the clinical translation of MSC therapy. Herein, we reviewed an overview of the research status of MSC transplantation after ICH in different species including rodents, swine, monkey, and human, and the challenges for MSC-mediated ICH recovery from pathological microenvironment have been summarized. Furthermore, some efficient strategies for the outcome improvement of MSC transplantation were proposed.

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Section: Optimizing Ich Microenvironmentmentioning

confidence: 99%

Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges

Gong

Hao

Wang

2021

Front. Cell. Neurosci.

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“…MSCs have emerged as a promising therapeutic tool in ICH. Although naïve MSCs are still the most common approach used to treat ICH, researches are being conducted to discover several methods to culture more functional MSCs, including pharmacologic pre-conditioning [ 54 ], alternative cell delivery approaches [ 55 – 57 ], genetic modification [ 58 , 59 ], physical methods [ 60 ], and modification of culture conditions [ 14 , 17 ]. Hypoxic preconditioning is a modification of culture conditions that have been shown to improve the therapeutic efficacy of stem cells in a model of atherosclerotic renal artery stenosis [ 61 ], spinal cord injury [ 62 ], ischemic stroke [ 18 , 63 , 64 ], acute lung injury [ 65 ], myocardial infarction [ 15 ], chronic liver injury [ 66 ], urethral injury [ 67 ], and ICH [ 14 , 17 ].…”

Section: Resultsmentioning

confidence: 99%

Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy

Liu

et al. 2021

Stem Cell Res Ther

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Background Intracerebral hemorrhage (ICH) is a major public health concern, and mesenchymal stem cells (MSCs) hold great potential for treating ICH. However, the quantity and quality of MSCs decline in the cerebral niche, limiting the potential efficacy of MSCs. Hypoxic preconditioning is suggested to enhance the survival of MSCs and augment the therapeutic efficacy of MSCs in ICH. MicroRNAs (miRNAs) are known to mediate cellular senescence. However, the precise mechanism by which miRNAs regulate the senescence of hypoxic MSCs remains to be further studied. In the present study, we evaluated whether hypoxic preconditioning enhances the survival and therapeutic effects of olfactory mucosa MSC (OM-MSC) survival and therapeutic effects in ICH and investigated the mechanisms by which miRNA ameliorates hypoxic OM-MSC senescence. Methods In the in vivo model, ICH was induced in mice by administration of collagenase IV. At 24 h post-ICH, 5 × 105 normoxia or hypoxia OM-MSCs or saline was administered intracerebrally. The behavioral outcome, neuronal apoptosis, and OM-MSC survival were evaluated. In the in vitro model, OM-MSCs were exposed to hemin. Cellular senescence was examined by evaluating the expressions of P16INK4A, P21, P53, and by β-galactosidase staining. Microarray and bioinformatic analyses were performed to investigate the differences in the miRNA expression profiles between the normoxia and hypoxia OM-MSCs. Autophagy was confirmed using the protein expression levels of LC3, P62, and Beclin-1. Results In the in vivo model, transplanted OM-MSCs with hypoxic preconditioning exhibited increased survival and tissue-protective capability. In the in vitro model, hypoxia preconditioning decreased the senescence of OM-MSCs exposed to hemin. Bioinformatic analysis identified that microRNA-326 (miR-326) expression was significantly increased in the hypoxia OM-MSCs compared with that of normoxia OM-MSCs. Upregulation of miR-326 alleviated normoxia OM-MSC senescence, whereas miR-326 downregulation increased hypoxia OM-MSC senescence. Furthermore, we showed that miR-326 alleviated cellular senescence by upregulating autophagy. Mechanistically, miR-326 promoted the autophagy of OM-MSCs via the PI3K signaling pathway by targeting polypyrimidine tract-binding protein 1 (PTBP1). Conclusions Our study shows that hypoxic preconditioning delays OM-MSC senescence and augments the therapeutic efficacy of OM-MSCs in ICH by upregulating the miR-326/PTBP1/PI3K-mediated autophagy.

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“…[ 45,47,54–56 ] Engineered hydrogels can release encapsulated therapeutics in a sustained manner, and therefore prolong drug presence around the target tissue, reducing the dose needed and avoiding systemic side effects. [ 55,57 ] Hydrogels can also be used to deliver cells into the ICH cavity, [ 58 ] enhancing cell survival by preventing mechanical damage to cells upon injection [ 59 ] and providing a permissive microenvironment for cell engraftment. [ 60 ]…”

Section: Hydrogels For Acute Brain Injury Repairmentioning

confidence: 99%

“…In ICH preclinical studies, hydrogels have been used as scaffolds for regeneration [ 45,46 ] or as delivery systems for therapeutics. [ 55–58 ] Approaches targeting unique aspects of ICH include the combination of hydrogels with previously tested drugs such as DFO [ 55 ] and MH, [ 57 ] which were delivered to the lesion for sustained action within a keratin‐based hydrogel. DFO was more effective in reducing iron deposition and brain edema when released from a hydrogel compared to DFO or hydrogel alone.…”

Section: Study Design: Combination Of Hydrogels With Therapeuticsmentioning

confidence: 99%

Regenerative Potential of Hydrogels for Intracerebral Hemorrhage: Lessons from Ischemic Stroke and Traumatic Brain Injury Research

Thomas

Louca

Bolan

et al. 2021

Adv Healthcare Materials

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Intracerebral hemorrhage (ICH) is a deadly and debilitating type of stroke, caused by the rupture of cerebral blood vessels. To date, there are no restorative interventions approved for use in ICH patients, highlighting a critical unmet need. ICH shares some pathological features with other acute brain injuries such as ischemic stroke (IS) and traumatic brain injury (TBI), including the loss of brain tissue, disruption of the blood–brain barrier, and activation of a potent inflammatory response. New biomaterials such as hydrogels have been recently investigated for their therapeutic benefit in both experimental IS and TBI, owing to their provision of architectural support for damaged brain tissue and ability to deliver cellular and molecular therapies. Conversely, research on the use of hydrogels for ICH therapy is still in its infancy, with very few published reports investigating their therapeutic potential. Here, the published use of hydrogels in experimental ICH is commented upon and how approaches reported in the IS and TBI fields may be applied to ICH research to inform the design of future therapies is described. Unique aspects of ICH that are distinct from IS and TBI that should be considered when translating biomaterial‐based therapies between disease models are also highlighted.

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Nanoparticle encapsulated core-shell hydrogel for on-site BMSCs delivery protects from iron overload and enhances functional recovery

Cited by 34 publications

References 46 publications

Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges

Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges

Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy

Regenerative Potential of Hydrogels for Intracerebral Hemorrhage: Lessons from Ischemic Stroke and Traumatic Brain Injury Research

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