Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing
Jianpei Xu1,2, Yinzhe Sun1,2, Yang You1,2
1Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
Abstract:
Mesenchymal stem cells (MSCs) experience substantial viability issues in the stroke infarct region, limiting their therapeutic efficacy and clinical translation. High levels of deadly reactive oxygen radicals (ROS) and proinflammatory cytokines (PC) in the infarct milieu kill transplanted MSCs, whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs' viability. Based on the intrinsic hormesis effects in cellular biology, we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC therapy. This system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective layer. In this system, extracellular ROS-scavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a micro-livable niche at the level of a single MSC for transplantation. Meanwhile, the infarct's inanimate milieu is transformed at the tissue level into a new living niche to facilitate healing. The engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 days. This vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.
Insights
Bioengineering mesenchymal stem cells (MSCs) with a microglial-inspired system significantly enhances their survival in stroke environments. This approach boosts MSC viability and improves stroke recovery, paving the way for better clinical translation.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Cell Therapy
Background:
- Mesenchymal stem cells (MSCs) show poor survival in stroke infarcts due to high reactive oxygen radicals (ROS) and proinflammatory cytokines (PC).
- Low levels of ROS and PC can stimulate MSCs, indicating a hormesis effect that can be leveraged for therapeutic benefit.
Purpose of the Study:
- To develop a microglia-inspired bioengineering system to enhance MSC viability and therapeutic efficacy in stroke treatment.
- To transform detrimental infarct conditions into a supportive microenvironment for transplanted MSCs.
Main Methods:
- Metabolic glycoengineered MSCs were bioorthogonally armed with microglial membrane-coated nanoparticles.
- An antioxidative extracellular protective layer was added to scavenge ROS and absorb PC.
- The engineered MSCs were transplanted into a stroke model to assess viability and therapeutic effects.
Main Results:
- Engineered MSCs demonstrated five times higher viability than natural MSCs at seven days post-transplantation.
- The bioengineered system created a micro-livable niche, buffering harmful infarct conditions.
- Superior therapeutic effects for stroke recovery were observed up to 28 days post-transplantation.
Conclusions:
- The microglia-inspired MSC bioengineering system effectively enhances MSC survival and function in the stroke infarct microenvironment.
- This vitality-augmented approach shows significant potential for accelerating MSC clinical translation and improving stroke recovery outcomes.
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