Bone progeria diminished the therapeutic effects of bone marrow mesenchymal stem cells on retinal degeneration

Chun-Lei Deng1, Cheng-Biao Hu2, Bao-Ying Wang3

  • 1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi, 710032, China; Central Laboratory, Taihe Hospital Affiliated to Xi'an Jiaotong University, Shiyan, Hubei, 442000, China.

Insights

Bone progeria impairs bone marrow mesenchymal stem cells (BMMSCs), diminishing their therapeutic potential for retinal degeneration. Aged SAMP6 mice showed retinal issues and their BMMSCs failed to treat degeneration.

Area of Science:

  • Gerontology
  • Ophthalmology
  • Stem Cell Biology

Background:

  • Cellular senescence is linked to retinal degeneration.
  • Bone marrow mesenchymal stem cells (BMMSCs) show therapeutic promise for retinal degeneration.
  • BMMSC function declines with age, but the impact of senescence on their therapeutic efficacy for retinal degeneration is unclear.

Purpose of the Study:

  • To investigate the effect of bone progeria on BMMSC therapeutic potential for retinal degeneration.
  • To evaluate BMMSC function in a senescence-accelerated mouse model.

Main Methods:

  • Utilized the senescence-accelerated mice-prone 6 (SAMP6) bone progeria model.
  • Induced retinal degeneration using MNU (N-methyl-N-nitrosourea).
  • Assessed BMMSC differentiation capacity and therapeutic effects in vivo.

Main Results:

  • SAMP6 mice exhibited retinal degeneration at 6 months.
  • BMMSCs from SAMP6 mice were unable to prevent MNU-induced retinal degeneration.
  • SAMP6 BMMSCs showed impaired differentiation compared to SAMR1 (control) BMMSCs.
  • BMMSCs from SAMR1 mice protected against MNU-induced retinal degeneration, upregulating NDRG2.

Conclusions:

  • Bone progeria significantly impairs BMMSC differentiation and therapeutic efficacy in retinal degeneration.
  • Senescence in BMMSCs compromises their ability to treat age-related retinal conditions.
  • NDRG2 may play a role in the protective effects of BMMSCs against retinal degeneration.