Regenerative patch technology

Imaging studies showed that the RPE cells appeared to integrate well into the eye and remained in place during follow-up tests to days after implantation. There were other indications the implants were proving beneficial. People with normal vision have the ability to focus their gaze on a single location. People with advanced AMD lose that ability. In this trial two of the patients went from having unstable fixation to stable fixation. These improvements were maintained in follow-up tests.

Proving its safety in humans is the first step in accomplishing that goal. While the results are encouraging the researchers caution that this was a very early stage clinical trial, with a small number of patients.

They say the next step is to continue to follow the four patients treated in this trial to see if there are any further changes to their vision, and to conduct a larger trial. We look forward to continuing our partnership and hopefully taking this encouraging start and making it even more successful in future clinical trials.

At CIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission. RPT was founded by Drs. Mark Humayun and David R. Image J software were used for quantitative data assessment. By comparing the RNA-seq data of ovaries from the cisplatin-injured rats and ORP treated rats, we listed out the upregulated and downregulated genes after treatment and performed the Metascape Gene List Analysis according to the literature In addition, ORP favors the development of vascular development after the damage.

A, B Bar graph across upregulated A or downregulated B gene lists, colored by p-values. C Schematic illustration of the mechanism underlying ORP treatment. Over the past decades, stem cell therapies have been proposed as a promising treatment for POI patients 41 , However, direct implantation of live cells may increase the risk of developing carcinoma and immune reactions.

Stem cell-derived secretome has been studied widely as an alternative treatment that restored serum level of FSH and E 2 in rats with iatrogenic POI 13 and augmented fertility in advanced reproductive aged animals The clinical application of these secretomes is still hampered by the issue of in vivo retention and sustainable release 45 , Patching up the tissues represented a sustained delivery manner for therapeutics GDF-9 can influence the differentiation of all follicle compartments, such as oocytes, granulosa cells and theca cells.

The ovaries from newborn GDF-9 knockout mice, isolated oocytes cannot recruit the surrounded OSCs to form follicles VEGF has been demonstrated to enable for arteriogenesis and improve development of granulosa cells by increasing the vessels of length, area, and branches HGF can inhibit apoptosis on OSCs and oocytes to improve vascular area growth, which contributes to ovarian function The SPS scaffold was a widely used material for reducing clinical relevant consequences of local wound bleeding and tissue adhesions ORP treatment protected ovarian function by rescue of female sex hormones, estrous cycling, follicle development and fertility.

However, it is unclear if ORP treatment rescued or prevented oocyte and granulosa cells from cell death or if there was regeneration of ovarian follicles subsequent to cisplatin-induced POI. So, therapies to improve oocyte quality and follicle development are the key to solve the problem. The rat model of chemically induced POI is a limitation of this work.

Pilot studies in a nonhuman primate may offer more information about the utility of ORP in humans. To understand the molecular biological mechanisms by which ORP therapies attenuate the adverse effects of cisplatin on ovarian reserve and function. Nevertheless, our present study presents a highly effective and clinically feasible new therapeutic strategy for POI. All the authors contributed to the overall scientific interpretation and edited the manuscript.

Additional data related to this paper may be requested from the authors. National Center for Biotechnology Information , U.

Journal List Theranostics v. Published online Aug Find articles by Sichen Zhang. Find articles by Dashuai Zhu. Find articles by Zhenhua Li. Find articles by Ke Huang. Find articles by Shiqi Hu. Find articles by Halle Lutz. Find articles by Mengjie Xie. Find articles by Xuan Mei. Find articles by Junlang Li. Find articles by Genevieve Neal-Perry. Find articles by Shaowei Wang.

Find articles by Ke Cheng. Author information Article notes Copyright and License information Disclaimer. China; Tel: ; Fax: ; E-mail: moc. Competing Interests: The authors have declared that no competing interest exists. Received Apr 15; Accepted Jul Abstract Rationale: Primary ovarian insufficiency POI normally occurs before age 40 and is associated with infertility.

Keywords: primary ovarian insufficiency, ovarian regenerative patch, regenerative medicine, mesenchymal stem cells, acellular therapy, fertility.

Introduction The prevalence of primary ovarian insufficiency POI is as high as 3. Open in a separate window. Figure 1. ORP Releasing experiment We measured the weight of ORP with an electronic scale after dehydration at each time point 0, 6, 12, 18, 24, 72, , h.

Examination of estrous cycles Vaginal smears were used to determine estrous cycling. ELISA for rat hormone Tail vein blood was collected from the rats at baseline and three weeks after treatments.

Immunohistochemistry IHC Ovarian cryo-sections were fixed by paraformaldehyde PFA solution, then blocked with blocking solution that contains 0.

Figure 2. Figure 3. Minimally invasive delivery of ORP to the rat ovaries In previous studies, therapeutics for ovary were usually delivered through laparotomy Figure 4. Biocompatibility of ORP in rats with POI Clinical trials and evidence-based medicine have confirmed the biocompatibility and safety of 37 , Figure 5.

Figure 6. Figure 7. Figure 8. Figure 9. Discussion Over the past decades, stem cell therapies have been proposed as a promising treatment for POI patients 41 , Supplementary Material Supplementary video S1. Click here for additional data file. Supplementary video S2. Supplementary video S3. Supplementary video S4. Author contributions K.

References 1. Incidence of premature ovarian failure. Obstet Gynecol. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis.

Primary ovarian insufficiency. The Lancet. Age at menopause, cause-specific mortality and total life expectancy. Nelson LM. Clinical practice. N Engl J Med. Impact of premature ovarian failure on mortality and morbidity among Chinese women. PLoS One. Maternal menopause as a predictor of anti-Mullerian hormone level and antral follicle count in daughters during reproductive age. Hum Reprod. Journal of the National Cancer Institute.

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