Biochemical and Biophysical Research Communications
Bone progeria diminished the therapeutic effects of bone marrow mesenchymal stem cells on retinal degeneration
Introduction
With the advancement of age, increasing elders are becoming susceptible to retinal degenerative diseases. These patients are presented as progressive deterioration of visual function and ultimate blindness, whereas confirmable treatments are still lacking [1]. Recent studies have reported that mesenchymal stem cell transplantation (MSCT) is beneficial for counteracting retinal degeneration. However, the regulatory factors of MSCT effects on retinal degeneration remain unknown.
Due to easily available and lower immunogenicity, bone marrow mesenchymal stem cells (BMMSCs) are widely used as feasible candidates in MSC transplantation (MSCT) [2]. Notably, BMMSCs used must comply with a set of criteria as quality control for therapy. Particularly, BMMSCs applied in MSCT should be derived from young donors, as senescence induces BMMSCs loss of stemness and may inhibit therapeutic effects [3]. Nevertheless, whether aging of BMMSCs affect their therapeutic effects on retinal degeneration remains unknown.
Senescence-accelerated mice (SAM) are a range of congenital evolution from the AKR/J strain [4]. SAMR1 mice demonstrate normal aging process, while SAMP6 mice exhibit rapidly developing bone progeria within a few months after birth [5]. We have previously established that BMMSCs from SAMP6 mice show functional impairments in vitro, compared to their SAMR1 counterparts [6,7]. The retinal phenotypes of SAMR1 and SAMP6 mice have not yet been evaluated.
In this study, we aimed to explore whether bone progeria affect therapeutic effects of BMMSCs on retinal degeneration. To address this issue, we applied SAMR1 mice, SAMP6 mice and a retinal degeneration mice model induced by N-methyl-N-nitrosourea (MNU), a DNA alkylating agent [8], as we previously used [9]. And we found that bone progeria diminished the therapeutic effects of BMMSC on retinal degeneration.
Section snippets
Animals
All experiments were conducted following the Guidelines of Intramural Animal Use and Care Committee of the Xi’an Jiaotong University and the ARRIVE guidelines. 4 and 6 months old SAMP6 and SAMR1 mice were purchased from the Council for SAM Research of Kyoto University, Japan. For RP modeling, 40 mg/kg MNU (Sigma, USA) was intraperitoneally injected to C57BL/6J mice. 6 h later, 1 μl BMMSC (1 × 107/ml) [10] were injected into the vitreous chambers [11]. The visual function detected by
Months old SAMP6 mice demonstrated retinal degeneration
SAMP6 mice have previously been documented as a premature bone aging model [16]. To explore the potential retinal temporal changes, 4 months and 6 months old SAMP6 mice were analyzed respectively compared to the age-matched SAMR1 mice. H&E staining and ERG analysis showed that there were no significant morphological and functional differences between SAMP6 and SAMR1 retinas at 4 months old (Fig 1A∼D). Nevertheless, H&E staining displayed that the outer nucleus layers (ONL) of 6-month old SAMP6
Discussion
Bone aging brings about degenerative skeletal diseases such as primary osteoporosis and osteoarthritis, meanwhile also impairing BMMSCs as important pathogenesis [17]. Studies have shown that MSCT have significant protective effects on retinal degenerative diseases [18], but whether senescence of MSC diminishes the therapeutic efficacy remains unknown. In this study, we have discovered that retina of 6 months old SAMP6 mice underwent premature degeneration, and BMMSCs from SAMP6 mice
Funding information
This work was supported by the National Natural Science Foundation of China (81870676), the Postdoctoral Innovative Talents Support Program of China (BX20190380), the Young Elite Scientist Sponsorship Program by CAST of China (2019QNRC001 to B.D.S.), and the General Program of China Postdoctoral Science Foundation (2019M663986).
Declaration of competing interest
The authors have declared that no competing interest exists.
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These authors contributed equally to this work.