Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon

Feichtinger, Michael; Barnea, Eytan R.; Nyachieo, Atunga; Brännström, Mats; Kim, S. Samuel

doi:10.1007/s10815-017-1051-y

Cited by 12 publications

(8 citation statements)

References 61 publications

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“…sPIF mostly regulates activated immune response without leading to immune suppression and preserves anti-pathogen action 22 . Thus, sPIF may limit damage and inflammation and promote tissue regeneration 28,30,34 .…”

Section: Discussionmentioning

confidence: 99%

“…Through an integrated local and systemic effect, sPIF protects against juvenile diabetes 26 , cardiovascular inflammation 27 , radiation-induced injury 28 , neuroinflammation, and neurotrauma in various animal models 29–32 . In addition, sPIF promotes ovarian allo-transplantation in transplantation models in primates and semi and allogeneic bone marrow transplantation 33,34 . Recently, sPIF was the subject of a successful University-initiated FDA Fast-Track-awarded Phase I clinical trial for autoimmune hepatitis and obtained Orphan Drug Designation (www.clinicaltrials.gov, NCT 02239562).…”

Section: Introductionmentioning

confidence: 99%

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sPIF promotes myoblast differentiation and utrophin expression while inhibiting fibrosis in Duchenne muscular dystrophy via the H19/miR-675/let-7 and miR-21 pathways

et al. 2019

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Duchenne muscular dystrophy (DMD) is a progressive, lethal, X-linked disease of skeletal and cardiac muscles caused by mutations in the dystrophin gene. Loss of dystrophin leads to muscle fiber damage and impairment of satellite cell asymmetric division, which are essential for muscle regeneration. These processes ultimately result in muscle wasting and the replacement of the degenerating muscles by fibrogenic cells, a process that leads to the generation of fibrotic tissues. Preimplantation factor (PIF) is an evolutionary conserved 15-amino acid peptide secreted by viable mammalian embryos. Synthetic PIF (sPIF) reproduces the protective/regenerative effects of the endogenous peptide in immune disorders and transplantation models. In this study, we demonstrated that sPIF treatment promoted mouse and human myoblast differentiation and inhibited the expression of collagen 1A1, collagen 1A2, and TGF-β in DMD patient-derived myoblasts. Additionally, sPIF increased the expression of utrophin, a homolog of dystrophin protein. sPIF effects were mediated via the upregulation of lncRNA H19 and miR-675 and downregulation of let-7. sPIF also inhibited the expression of miR-21, a major fibrosis regulator. The administration of sPIF in mdx mice significantly decreased serum creatine kinase and collagen I and collagen IV expression in the diaphragm, whereas it increased utrophin expression in the diaphragm, heart and quadriceps muscles. In conclusion, sPIF promoted the differentiation of DMD myoblasts, increased utrophin expression via the H19/miRNA-675/let-7 pathway, and reduced muscle fibrosis possibly via the upregulation of miR-675 and inhibition of miR-21 expression. These findings strongly support pursuing sPIF as a potential therapeutic agent for DMD. Moreover, the completion of an sPIF phase I safety trial will further promote the use of sPIF for the treatment of muscular dystrophies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

sPIF promotes myoblast differentiation and utrophin expression while inhibiting fibrosis in Duchenne muscular dystrophy via the H19/miR-675/let-7 and miR-21 pathways

et al. 2019

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“…1 The recent discovery of preimplantation factor (PIF), a natural immunosuppressive and immunomodulating peptide that prevents maternal rejection of an allogeneic fetus, may lead to its development as an immunosuppressant without the risks of severe infections resulting from immune compromise. 6,7 Secreted by the embryo and later by the placenta, PIF creates maternal tolerance to an allogeneic embryo. In women who have autoimmune diseases, PIF often leads to spontaneous improvement during pregnancy and lowers the risk of postpartum f lares.…”

mentioning

confidence: 99%

“…In women who have autoimmune diseases, PIF often leads to spontaneous improvement during pregnancy and lowers the risk of postpartum f lares. Results of PIF treatment in preclinical models of ovarian transplantation in baboons 6 and murine GVHD 7 have been promising.…”

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confidence: 99%

Progress in Immunosuppressive Agents for Solid-Organ Transplantation

Zhang¹,

Vierling²

2019

Texas Heart Institute Journal

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“…The term “artificial ovary” was also used to describe a tissue‐based hormone therapy that restores steroid hormones in patients with POF and menopausal women (David et al, ; Day et al, ; Feichtinger, Barnea, Nyachieo, Brannstrom, & Kim, ; Laronda et al, ; Sittadjody et al, ).…”

Section: Introductionmentioning

confidence: 99%

A new possibility in fertility preservation: The artificial ovary

Cho

Kim

Noh

et al. 2019

J Tissue Eng Regen Med

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Conventional fertility preservation methods such as oocyte or embryo cryopreservation are currently insufficient to treat including those patients with prepubertal cancer and premature ovarian failure. Ovarian tissue cryopreservation presents as an alternative but has limitations with a potential risk of reintroducing malignant cells in patients who recover from cancer, those of chemotherapy prior to tissue cryopreservation. The so called “artificial ovary” aims to resolve this issue by transplanting isolated follicles with or without a biological scaffold. The artificial ovary may also offer an effective alternative option for those who cannot benefit from traditional assisted reproductive techniques such as in vitro fertilisation. To date, in animal studies and human trial, the artificial ovary restored endocrine function, achieved in vivo follicular development, and resulted in successful pregnancies. However, development of a technique for higher follicular recovery rate and a more optimised design of delivery scaffold, better transplantation techniques to prevent postsurgical ischemia, and consideration for genetic safety are required for safer and consistent human clinical applications. Ideas from different transplantation surgeries (e.g., entire ovary, ovarian cortex, and transplantation with tissue‐engineered products) can be applied to enhance the efficacy of artificial ovarian transplantation. For the better application of artificial ovary, a deeper understanding of mechanical and biochemical properties of the ovary and folliculogenesis after cryopreservation, transplantation with or without scaffold, and development of sophisticated in vivo imaging techniques of transplanted artificial ovary need to precede its efficient clinical application.

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Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon

Abstract: Organ rejection after allogeneic ovarian transplantation was prevented using PIF as monotherapy for the first time and no side effects were recorded. The study suggests the clinical feasibility of ovarian allotransplantation to obtain ovarian function.

Cited by 12 publications

References 61 publications

sPIF promotes myoblast differentiation and utrophin expression while inhibiting fibrosis in Duchenne muscular dystrophy via the H19/miR-675/let-7 and miR-21 pathways

sPIF promotes myoblast differentiation and utrophin expression while inhibiting fibrosis in Duchenne muscular dystrophy via the H19/miR-675/let-7 and miR-21 pathways

Progress in Immunosuppressive Agents for Solid-Organ Transplantation

A new possibility in fertility preservation: The artificial ovary

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