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Ultrasound-guided Intracardiac Injection of Human Mesenchymal Stem Cells to Increase Homing to the Intestine for Use in Murine Models of Experimental Inflammatory Bowel Diseases
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Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in

Jiawei Guo1, Fuxiao Wang2, Yan Hu2

  • 1Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; Department of Orthopedics Trauma, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.

Cell Reports. Medicine
|January 5, 2023
PubMed

Insights

Inflammatory bowel diseases cause bone loss by altering bone marrow stem cell differentiation. Targeted exosome therapy can restore bone formation and quality in colitis models.

Area of Science:

  • Biomedical Science
  • Cell Biology
  • Bone Biology

Background:

  • Systematic bone loss is a common complication of inflammatory bowel diseases (IBDs), with unclear pathogenesis and treatment strategies.
  • Experimental colitis models show decreased bone mass, reduced bone formation rates, and fewer osteoblasts.
  • Bone marrow mesenchymal stem/stromal cells (BMSCs) from colitis models exhibit a shift towards adipogenesis over osteogenesis.

Purpose of the Study:

  • To investigate the mechanisms underlying bone loss in inflammatory bowel diseases.
  • To explore the potential of exosome-based therapy for treating bone loss associated with IBD.
  • To evaluate the efficacy of bone-targeted drug delivery systems in restoring bone health.

Main Methods:

  • Established experimental colitis mouse models using dextran sulfate sodium and IL-10 knockout induced with piroxicam.
  • Analyzed bone mass, quality, and cellularity in femur of colitis mice.
  • Utilized RNA sequencing to identify molecular pathways affected in BMSCs.
  • Developed and administered engineered exosomes carrying a Wnt agonist via intravenous injection.

Main Results:

  • Colitis mice exhibited significantly decreased bone mass and quality, with reduced bone formation and osteoblast numbers.
  • BMSCs from colitis mice showed impaired osteogenic differentiation and promoted adipogenesis.
  • Serum from IBD patients induced adipogenesis in human BMSCs.
  • Engineered exosomes successfully delivered Wnt agonist to bone, alleviating bone loss, promoting bone formation, and accelerating fracture healing in colitis mice.

Conclusions:

  • The inflammatory microenvironment in IBD alters BMSC commitment, leading to reduced bone quantity and quality.
  • Targeted delivery of Wnt agonists via exosomes can effectively redirect BMSC differentiation towards osteogenesis.
  • Exosome-based therapy represents a promising strategy for rescuing bone loss and improving bone health in IBD patients.
Keywords:
exosomeinflammatory bowel diseasesmesenchymal stem cellosteoblastic formationosteogenesis

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