Ultrasound Targeted Microbubble Destruction Promotes the Therapeutic Effect of HUMSC Transplantation on Glaucoma-Caused Optic Nerve Injury in Rabbits

Abstract

Purpose The purpose of this study was to explore the therapeutic effect of human umbilical cord mesenchymal stem cell (HUMSC) transplantation alone or assisted with ultrasound targeted microbubble destruction (UTMD) on optic neuropathy in a novel and practical model of experimental glaucoma in rabbits. Methods Eight New Zealand white healthy rabbits were used as the control group (group A). Twenty-four experimental glaucomatous rabbits were established as described previously and randomly divided into three groups: (1) received no treatment (group B); (2) received intravitreal transplantation of HUMSCs (group C); and (3) received UTMD-assisted intravitreal transplantation of HUMSCs (group D). After 4 weeks of treatment, the distribution of HUMSCs, retinal thickness, layer structure, retinal ganglion cells (RGCs), and their axons were examined. Results After 4 weeks of treatment, HUMSCs were successfully scattered under the retina. HUMSC transplantation significantly increased the regeneration of RGCs and their axons, and restored the retinal structure in glaucomatous rabbits. Moreover, the application of UTMD enhances HUMSC distribution and achieved more significant therapeutic effect. Conclusions Intravitreal transplantation of HUMSCs effectively repaired glaucomatous optic nerve injury, and UTMD enhanced the successful delivery of HUMSCs into injured retina, promoting its therapeutic effects remarkably. Translational Relevance This study demonstrated that HUMSC transplantation repaired the glaucoma-caused nerve injury significantly and the combination of UTMD can augment the therapeutic effect further, which has important clinical guiding significance for the development of therapeutic strategies of glaucoma.

Mesenchymal stem cells for repairing glaucomatous optic nerve

“…Significant progress has been made since this goal was set a decade ago. It is likely that multiple technologies for restoring vision will be clinically applied within the next decade (Table 1) [6,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] .…”

“…Human-derived MSCs promoted sustained neuroprotection and regeneration of RGCs after optic nerve injury hUC-MSCs [45] UTMD enhanced target-specific gene delivery, thus improving the effect of therapy UTMD can remarkably enhance the therapeutic effect of hUC-MSCs hPMSCs [46] UBA2 played a key role in activating the Wnt/β-catenin signaling pathway…”

Targeted Microbubbles for Drug, Gene, and Cell Delivery in Therapy and Immunotherapy

“…These biological effects lead to enhanced cellular delivery through mechanisms such as drug convection and diffusion through the pores (4-70 kDa) and endocytosis (70-500 kDa) [33][34][35]38]. Following their clinical translation as ultrasound imaging contrast agents, MB formulations have been engineered as ultrasound-responsive carriers to promote and enhance the local delivery and uptake of a wide variety of drugs [8][9][10][11], genes [12][13][14], and cells [15][16][17][18][19][20] for various therapeutic applications. Many of these applications include the delivery of therapeutic agents to treat the brain [19][20][21][22][23], heart [15,[24][25][26], and cancer [27][28][29].…”