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UrduBACKGROUND
AIM
To enhance the efficiency and therapeutic efficacy of MSCs, an in vivo-like 3D culture condition was applied.
METHODS
MSCs were cultured on polystyrene (2D) or in a gellan gum-based 3D system. In vitro, prostaglandin-endoperoxide synthase 2, indoleamine-2,3-dioxygenase, heme oxygenase 1, and prostaglandin E synthase gene expression was quantified by quantitative real-time polymerase chain reaction. MSCs were incubated with lipopolysaccharide (LPS)-treated mouse splenocytes, and prostaglandin E2 and tumor necrosis factor-alpha levels were measured by enzyme linked immunosorbent assay. In vivo, LPS was injected into the lateral ventricle of mouse brain, and MSCs were administered intravenously the next day. Animals were sacrificed and analyzed on days 2 and 6.
RESULTS
Gellan gum polymer-based 3D culture significantly increased expression of octamer-binding transcription factor 4 and Nanog homeobox stemness markers in human MSCs compared to 2D culture. This 3D environment also heightened expression of cyclooxygenase-2 and heme-oxygenase 1, enzymes known for immunomodulatory functions, including production of prostaglandins and heme degradation, respectively. MSCs in 3D culture secreted more prostaglandin E2 and effectively suppressed tumor necrosis factor-alpha release from LPS-stimulated splenocytes and surpassed the efficiency of MSCs cultured in 2D. In a murine neuroinflammation model, intravenous injection of 3D-cultured MSCs significantly reduced ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression, mitigating chronic inflammation more effectively than 2D-cultured MSCs.
CONCLUSION
The microenvironment established in 3D culture serves as an in vivo mimetic, enhancing the immunomodulatory function of MSCs. This suggests that engineered MSCs hold significant promise a potent tool for cell therapy.
Key Words: Mesenchymal stromal cells; Three-dimensional culture; Immunomodulatory function; Neuroinflammation; Cell therapy
Core Tip: Clinical trials utilizing mesenchymal stromal cells (MSCs) have been on the rise, but several barriers to broader adoption of MSCs as therapeutics remain to be addressed. Our study presents compelling evidence demonstrating the remarkable enhancement of immunomodulatory capabilities in functional polymer-based MSCs through three-dimensional culture. We specifically applied these optimized MSCs to a brain inflammation model and found a prolonged and more potent anti-inflammatory effect in vivo compared to conventionally cultured MSCs. The polymer-based three-dimensional cultures we propose could be an easy tool for mass culture for clinical applications.
- Citation: Kim OH, Kang H, Chang ES, Lim Y, Seo YJ, Lee HJ. Extended protective effects of three dimensional cultured human mesenchymal stromal cells in a neuroinflammation model. World J Stem Cells 2025; 17(1): 101485
- URL: https://www.wjgnet.com/1948-0210/full/v17/i1/101485.htm
- DOI: https://dx.doi.org/10.4252/wjsc.v17.i1.101485
