Autologous activated platelet-rich plasma injection into adult human ovary tissue: molecular mechanism, analysis, and discussion of reproductive response

E Scott Sills, Samuel H Wood, E Scott Sills, Samuel H Wood

Abstract

In clinical infertility practice, one intractable problem is low (or absent) ovarian reserve which in turn reflects the natural oocyte depletion associated with advancing maternal age. The number of available eggs has been generally thought to be finite and strictly limited, an entrenched and largely unchallenged tenet dating back more than 50 years. In the past decade, it has been suggested that renewable ovarian germline stem cells (GSCs) exist in adults, and that such cells may be utilized as an oocyte source for women seeking to extend fertility. Currently, the issue of whether mammalian females possess such a population of renewable GSCs remains unsettled. The topic is complex and even agreement on a definitive approach to verify the process of 'ovarian rescue' or 're-potentiation' has been elusive. Similarities have been noted between wound healing and ovarian tissue repair following capsule rupture at ovulation. In addition, molecular signaling events which might be necessary to reverse the effects of reproductive ageing seem congruent with changes occurring in tissue injury responses elsewhere. Recently, clinical experience with such a technique based on autologous activated platelet-rich plasma (PRP) treatment of the adult human ovary has been reported. This review summarizes the present state of understanding of the interaction of platelet-derived growth factors with adult ovarian tissue, and the outcome of human reproductive potential following PRP treatment.

Keywords: aging; fertility; menopause; ovary; reproduction.

Conflict of interest statement

E.S.S. holds a provisional U.S. patent for process and treatment using ovarian PRP.

© 2019 The Author(s).

Figures

Figure 1. Recruitment and growth of oocytes,…
Figure 1. Recruitment and growth of oocytes, from PGC stage through mature follicle, illustrating various growth factors mediating development
Known components of this sequence include granulosa precursors (red), theca compartment (blue), and germ cells (black). Upstream contributions by ovarian stem cells (OSC) may be possible under conditions enabled by growth factors released by platelet-rich plasma (PRP-GFs). Other relevant regulators are BMP2, BMP6, and BMP8β, which are involved in cytokine–cytokine receptor interactions; and Transforming growth factor β (TGF-β), which activates various substrates and regulatory proteins inducing transcription of genes for differentiation, chemotaxis, and proliferation. Later direction is under control of BMP15, a paracrine signal exclusively expressed in ovarian tissue which is involved in oocyte and follicular growth, as well as GDF9, a down-regulator of inhibin-A and promoter of further follicular maturation.
Figure 2. Proposed mechanism of action for…
Figure 2. Proposed mechanism of action for alteration of adult ovarian function by application of activated PRP
Autologous activated PRP sample generates an enriched platelet (PLT) substrate collected by peripheral venipuncture. PLT combination with calcium gluconate achieves activation of α granules [red circles], which subsequently initiates release of at least three classes of molecular mediators. These include chemokines such as Interleukin-1β (IL-1β), a central inflammatory mediator involved in cell proliferation, differentiation, and apoptosis; Interleukin-8 (IL-8, also known as neutrophil chemotactic factor) which coordinates migration toward sites of injury or infection and is a promoter of angiogenesis and improved tissue perfusion; Platelet factor 4 (PF4), a versatile chemotactic protein with high affinity for heparin, involved in platelet aggregation and selective antimicrobial activity; Ligand of CD40 (CD-40L), a potent inducer of inflammatory processes by enhancing interactions among platelets, leukocytes, and endothelium; a protein known as Regulated after Activation of Normal T-cell Expressed and Secreted (RANTES), itself a useful marker for PLT activation which strongly attracts monocytes; Macrophage inflammatory protein 1-α (MIP-1α), which conditionally triggers migration and signaling cascades to mediate cell survival and proliferation; Platelet-associated cellular mitogens include TGF-β, which activates different downstream substrates and regulatory proteins inducing transcription of multiple target genes for differentiation, chemotaxis, proliferation and activation of immune system cells; Vascular endothelial growth factor (VEGF), a signal protein stimulating blood vessel formation; Insulin like growth factors (IGFs) a group of proteins with close homology to insulin required for cell stimulation and communication with the local environment; Platelet derived growth factor (PDGF), critical in growth of blood vessels from extant nearby capillaries, mitogenesis and proliferation of mesenchymal cells including fibroblasts, osteoblasts, tenocytes, vascular SMCs and mesenchymal stem cells; epidermal growth factor (EGF), a central element in cellular proliferation, differentiation, and survival; Basic fibroblast growth factor (bFGF), a mediator with broad mitogenic and cell survival activities, and is involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion function. Platelet expressed antigens include Platelet endothelial cell adhesion molecule (PECAM), which plays a key role in removing aged neutrophils from circulation; P-selectin which contributes to initial recruitment of leukocytes to injury sites during inflammation; Glycoprotein IIb/IIIa, part of the integrin complex found on platelets aiding in platelet activation; and Glycoprotein Ib and IX (GPIb/IX) which binds von Willebrand factor, allowing platelet adhesion and platelet plug formation at sites of vascular injury. PRP is placed inside the adult ovary (by direct ultrasound-guided needle injection) thus permitting these signaling elements access to ovarian stem cells (OSCs) as discussed by Johnson et al. (2004). PLT-derived moieties then trigger or enable differentiation of these OSCs. Subsequently, reduced serum FSH and/or higher post-treatment levels of serum AMH have been observed clinically, consistent with improved or ‘re-potentiated’ ovarian function.

References

    1. Sills E.S., Alper M.M. and Walsh A.P. (2009) Ovarian reserve screening in infertility: practical applications and theoretical directions for research. Eur. J. Obstet. Gynecol. Reprod. Biol. 146, 30–36 10.1016/j.ejogrb.2009.05.008
    1. Hsueh A.J., Kawamura K., Cheng Y. and Fauser B.C. (2015) Intraovarian control of early folliculogenesis. Endocr. Rev. 36, 1–24 10.1210/er.2014-1020
    1. Robin C., Ottersbach K., de Bruijn M., Ma X., van der Horn K. and Dzierzak E. (2003) Developmental origins of hematopoietic stem cells. Oncol. Res. 13, 315–321 10.3727/096504003108748519
    1. Hummitzsch K., Anderson R.A., Wilhelm D., Wu J., Telfer E.E., Russell D.L.. et al. (2015) Stem cells, progenitor cells, and lineage decisions in the ovary. Endocr. Rev. 36, 65–91 10.1210/er.2014-1079
    1. Guigon C.J. and Cohen-Tannoudji M. (2011) Reconsidering the roles of female germ cells in ovarian development and folliculogenesis. Biol. Aujourdhui 205, 223–233 10.1051/jbio/2011022
    1. Bukovsky A., Caudle M.R., Svetlikova M., Wimalasena J., Ayala M.E. and Dominguez R. (2005) Oogenesis in adult mammals, including humans: a review. Endocrine 26, 301–316 10.1385/ENDO:26:3:301
    1. Parte S., Bhartiya D., Telang J., Daithankar V., Salvi V., Zaveri K.. et al. (2011) Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary. Stem Cells Dev. 20, 1451–1464 10.1089/scd.2010.0461
    1. Virant-Klun I., Zech N., Rozman P., Vogler A., Cvjeticanin B., Klemenc P.. et al. (2008) Putative stem cells with an embryonic character isolated from the ovarian surface epithelium of women with no naturally present follicles and oocytes. Differentiation 76, 843–856 10.1111/j.1432-0436.2008.00268.x
    1. Motta P.M. and Makabe S. (1986) Elimination of germ cells during differentiation of the human ovary: an electron microscopic study. Eur. J. Obstet. Gynecol. Reprod. Biol. 22, 271–286 10.1016/0028-2243(86)90115-2
    1. Kerr J.B., Duckett R., Myers M., Britt K.L., Mladenovska T. and Findlay J.K. (2006) Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply. Reproduction 132, 95–109 10.1530/rep.1.01128
    1. White Y.A., Woods D.C., Takai Y., Ishihara O., Seki H. and Tilly J.L. (2012) Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat. Med. 18, 413–421 10.1038/nm.2669
    1. Zuckerman S. (1951) The number of oocytes in the mature ovary. Recent Prog. Horm. Res. 6, 63–109
    1. Johnson J., Canning J., Kaneko T., Pru J.K. and Tilly J.L. (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428, 145–150 10.1038/nature02316
    1. Zou K., Yuan Z., Yang Z.. et al. (2009) Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat. Cell Biol. 11, 631–636 10.1038/ncb1869
    1. Zhou L., Wang L., Kang J.X.. et al. (2014) Production of fat-1 transgenic rats using a post-natal female germline stem cell line. Mol. Hum. Reprod. 20, 271–281 10.1093/molehr/gat081
    1. Johnson J., Bagley J., Skaznik-Wikiel M.. et al. (2005) Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 122, 303–315 10.1016/j.cell.2005.06.031
    1. Eggan K., Jurga S., Gosden R., Min I.M. and Wagers A.J. (2006) Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature 441, 1109–1114 10.1038/nature04929
    1. Lee H.J., Selesniemi K., Niikura Y.. et al. (2007) Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure. J. Clin. Oncol. 25, 3198–3204 10.1200/JCO.2006.10.3028
    1. Notarianni E. (2011) Reinterpretation of evidence advanced for neo-oogenesis in mammals, in terms of a finite oocyte reserve. J. Ovarian Res. 4, 1 10.1186/1757-2215-4-1
    1. Zulli A., Rai S., Buxton B.F., Burrell L.M. and Hare D.L. (2008) Co-localization of angiotensin-converting enzyme 2-, octomer-4- and CD34-positive cells in rabbit atherosclerotic plaques. Exp. Physiol. 93, 564–569 10.1113/expphysiol.2007.040204
    1. Brännström M., Mayrhofer G. and Robertson S.A. (1993) Localization of leukocyte subsets in the rat ovary during the periovulatory period. Biol. Reprod. 48, 277–286 10.1095/biolreprod48.2.277
    1. Best C.L., Pudney J., Welch W.R., Burger N. and Hill J.A. (1996) Localization and characterization of white blood cell populations within the human ovary throughout the menstrual cycle and menopause. Hum. Reprod. 11, 790–797 10.1093/oxfordjournals.humrep.a019256
    1. Samy E.T., Parker L.A., Sharp C.P. and Tung K.S. (2005) Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node. J. Exp. Med. 202, 771–781 10.1084/jem.20041033
    1. Samy E.T., Setiady Y.Y., Ohno K., Pramoonjago P., Sharp C. and Tung K.S. (2006) The role of physiological self-antigen in the acquisition and maintenance of regulatory T-cell function. Immunol. Rev. 212, 170–184 10.1111/j.0105-2896.2006.00404.x
    1. Alard P., Thompson C., Agersborg S.S.. et al. (2001) Endogenous oocyte antigens are required for rapid induction and progression of autoimmune ovarian disease following day-3 thymectomy. J. Immunol. 166, 4363–4369 10.4049/jimmunol.166.7.4363
    1. Reizel Y., Itzkovitz S., Adar R.. et al. (2012) Cell lineage analysis of the mammalian female germline. PLoS Genet. 8, e1002477 10.1371/journal.pgen.1002477
    1. Henderson S.A. and Edwards R.G. (1968) Chiasma frequency and maternal age in mammals. Nature 218, 22–28 10.1038/218022a0
    1. Pacchiarotti J., Maki C., Ramos T.. et al. (2010) Differentiation potential of germ line stem cells derived from the postnatal mouse ovary. Differentiation 79, 159–170 10.1016/j.diff.2010.01.001
    1. Zhang Y., Yang Z., Yang Y.. et al. (2011) Production of transgenic mice by random recombination of targeted genes in female germline stem cells. J. Mol. Cell Biol. 3, 132–141 10.1093/jmcb/mjq043
    1. Zhang Y. and Wu J. (2009) Molecular cloning and characterization of a new gene, Oocyte-G1. J. Cell. Physiol. 218, 75–83 10.1002/jcp.21569
    1. Imudia A.N., Wang N., Tanaka Y., White Y.A., Woods D.C. and Tilly J.L. (2013) Comparative gene expression profiling of adult mouse ovary-derived oogonial stem cells supports a distinct cellular identity. Fertil. Steril. 100, 1451–1458 10.1016/j.fertnstert.2013.06.036
    1. Park E.S., Woods D.C. and Tilly J.L. (2013) Bone morphogenetic protein 4 promotes mammalian oogonial stem cell differentiation via Smad1/5/8 signaling. Fertil. Steril. 100, 1468–1475 10.1016/j.fertnstert.2013.07.1978
    1. Lawson K.A., Dunn N.R., Roelen B.A.. et al. (1999) Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev. 13, 424–436 10.1101/gad.13.4.424
    1. Childs A.J., Kinnell H.L., Collins C.S.. et al. (2010) BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis. Stem Cells 28, 1368–1378 10.1002/stem.440
    1. Le Bouffant R., Souquet B., Duval N.. et al. (2011) Msx1 and Msx2 promote meiosis initiation. Development 138, 5393–5402 10.1242/dev.068452
    1. Abban G. and Johnson J. (2009) Stem cell support of oogenesis in the human. Hum. Reprod. 24, 2974–2978 10.1093/humrep/dep281
    1. Castrillon D.H., Quade B.J., Wang T.Y., Quigley C. and Crum C.P. (2000) The human VASA gene is specifically expressed in the germ cell lineage. Proc. Natl Acad. Sci. U.S.A. 97, 9585–9590 10.1073/pnas.160274797
    1. Zou K., Hou L., Sun K., Xie W. and Wu J. (2011) Improved efficiency of female germline stem cell purification using fragilis-based magnetic bead sorting. Stem Cells Dev. 20, 2197–2204 10.1089/scd.2011.0091
    1. Wang H., Jiang M., Bi H.. et al. (2014) Conversion of female germline stem cells from neonatal and prepubertal mice into pluripotent stem cells. J. Mol. Cell Biol. 6, 164–171 10.1093/jmcb/mju004
    1. Xie W., Wang H. and Wu J. (2014) Similar morphological and molecular signatures shared by female and male germline stem cells. Sci. Rep. 4, 5580 10.1038/srep05580
    1. Møllgård K., Jespersen A., Lutterodt M.C., Yding Andersen C., Høyer P.E. and Byskov A.G. (2010) Human primordial germ cells migrate along nerve fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge. Mol. Hum. Reprod. 16, 621–631 10.1093/molehr/gaq052
    1. Bendel-Stenzel M., Anderson R., Heasman J. and Wylie C. (1998) The origin and migration of primordial germ cells in the mouse. Semin. Cell Dev. Biol. 9, 393–400 10.1006/scdb.1998.0204
    1. De Felici M. (2010) Germ stem cells in the mammalian adult ovary: considerations by a fan of the primordial germ cells. Mol. Hum. Reprod. 16, 632–636 10.1093/molehr/gaq006
    1. Shin D.M., Zuba-Surma E.K., Wu W., Ratajczak J., Wysoczynski M., Ratajczak M.Z.. et al. (2009) Novel epigenetic mechanisms that control pluripotency and quiescence of adult bone marrow-derived Oct4(þ) very small embryonic-like stem cells. Leukemia 23, 2042–2051 10.1038/leu.2009.153
    1. Kucia M., Maj M., Mierzejewska K., Shin D.M., Ratajczak J. and Ratajczak M.Z. (2013) Challenging dogmas - or how much evidence is necessary to claim that there is a direct developmental and functional link between the primordial germ cell (PGC) lineage and hematopoiesis? Blood 122, 21
    1. Havens A.M., Shiozawa Y., Jung Y., Sun H., Wang J., McGee S.. et al. (2013) Human very small embryonic-like cells generate skeletal structures, in vivo. Stem Cells Dev. 22, 622–630 10.1089/scd.2012.0327
    1. Wojakowski W., Ratajczak M.Z. and Tendera M. (2010) Mobilization of very small embryonic-like stem cells in acute coronary syndromes and stroke. Herz 35, 467–472 10.1007/s00059-010-3389-0
    1. Sovalat H., Scrofani M., Eidenschenk A., Pasquet S., Rimelen V. and Hénon P. (2011) Identification and isolation from either adult human bone marrow or G-CSF-mobilized peripheral blood of CD34(+)/CD133(+)/CXCR4(+)/Lin(-)CD45(-) cells, featuring morphological, molecular, and phenotypic characteristics of very small embryonic-like (VSEL) stem cells. Exp. Hematol. 39, 495–505
    1. Drukała J., Paczkowska E., Kucia M., Młyńska E., Krajewski A., Machaliński B.. et al. (2012) Stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients after skin burn injury. Stem Cell Rev. 8, 184–194 10.1007/s12015-011-9272-4
    1. Bhartiya D., Anand S., Patel H. and Parte S. (2017) Making gametes from alternate sources of stem cells: past, present and future. Reprod. Biol. Endocrinol. 15, 89 10.1186/s12958-017-0308-8
    1. Byskov A.G., Høyer P.E., Yding Andersen C., Kristensen S.G., Jespersen A. and Møllgård K. (2011) No evidence for the presence of oogonia in the human ovary after their final clearance during the first two years of life. Hum. Reprod. 26, 2129–2139 10.1093/humrep/der145
    1. Bhartiya D., Unni S., Parte S. and Anand S. (2013) Very small embryonic-like stem cells: implications in reproductive biology. Biomed. Res. Int. 2013, 682326 10.1155/2013/682326
    1. Ratajczak M.Z., Zuba-Surma E., Wojakowski W., Suszynska M., Mierzejewska K., Liu R.. et al. (2014) Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology: recent pros and cons in the midst of a lively debate. Leukemia 28, 473–484 10.1038/leu.2013.255
    1. Bhartiya D., Hinduja I., Patel H. and Bhilawadikar R. (2014) Making gametes from pluripotent stem cells–a promising role for very small embryonic-like stem cells. Reprod. Biol. Endocrinol. 12, 114 10.1186/1477-7827-12-114
    1. Ratajczak M. (2012) Igf2-H19, an imprinted tandem gene, is an important regulator of embryonic development, a guardian of proliferation of adult pluripotent stem cells, a regulator of longevity, and a ‘passkey’ to cancerogenesis. Folia Histochem. Cytobiol. 50, 171–179 10.5603/FHC.2012.0026
    1. Monti M., Imberti B., Bianchi N., Pezzotta A., Morigi M., Del Fante C.. et al. (2017) A novel method for isolation of pluripotent stem cells from human umbilical cord blood. Stem Cells Dev. 26, 1258–1269 10.1089/scd.2017.0012
    1. Binelli M. and Murphy B.D. (2010) Coordinated regulation of follicle development by germ and somatic cells. Reprod. Fertil. Dev. 22, 1–12 10.1071/RD09218
    1. Byskov A.G. (1986) Differentiation of mammalian embryonic gonad. Physiol. Rev. 66, 71–117 10.1152/physrev.1986.66.1.71
    1. Auersperg N., Wong A.S., Choi K.C., Kang S.K. and Leung P.C. (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr. Rev. 22, 255–288
    1. Hummitzsch K., Irving-Rodgers H.F., Hatzirodos N.. et al. (2013) A new model of development of the mammalian ovary and follicles. PLoS ONE 8, e55578 10.1371/journal.pone.0055578
    1. Rodgers R.J. and Hummitzsch K. (2014) New Model of Formation of the Ovary, Robinson Research Institute,
    1. Kenngott R.A., Vermehren M., Ebach K. and Sinowatz F. (2013) The role of ovarian surface epithelium in folliculogenesis during fetal development of the bovine ovary: a histological and immunohistochemical study. Sex Dev. 7, 180–195 10.1159/000348881
    1. Szotek P.P., Chang H.L., Brennand K.. et al. (2008) Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics. Proc. Natl. Acad. Sci. U.S.A. 105, 12469–12473 10.1073/pnas.0805012105
    1. Usongo M. and Farookhi R. (2012) β-Catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells. BMC Dev. Biol. 12, 17 10.1186/1471-213X-12-17
    1. Bernard P., Fleming A., Lacombe A., Harley V.R. and Vilain E. (2008) Wnt4 inhibits β-catenin/TCF signalling by redirecting β-catenin to the cell membrane. Biol. Cell 100, 167–177 10.1042/BC20070072
    1. Rastetter R.H., Bernard P., Palmer J.S.. et al. (2014) Marker genes identify three somatic cell types in the fetal mouse ovary. Dev. Biol. 394, 242–252 10.1016/j.ydbio.2014.08.013
    1. Gamwell L.F., Collins O. and Vanderhyden B.C. (2012) The mouse ovarian surface epithelium contains a population of LY6A (SCA-1) expressing progenitor cells that are regulated by ovulation-associated factors. Biol. Reprod. 87, 80
    1. Martin P. (1997) Wound healing—aiming for perfect skin regeneration. Science 276, 75–81 10.1126/science.276.5309.75
    1. Hensley K. and Floyd R.A. (2002) Reactive oxygen species and protein oxidation in aging: a look back, a look ahead. Arch. Biochem. Biophys. 397, 377–383 10.1006/abbi.2001.2630
    1. Mannaioni P.F., Di Bello G.M. and Masini E. (1997) Platelets and inflammation: role of platelet-derived growth factor, adhesion molecules and histamine. Inflamm. Res. 46, 4–18 10.1007/PL00000158
    1. Anitua E., Andía I., Ardanza B., Nurden P. and Nurden A. (2004) Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb. Haemost. 91, 4–15 10.1160/TH03-07-0440
    1. Crowley S.T., Dempsey E.C., Horwitz K.B. and Horwitz L.D. (1994) Platelet-induced vascular smooth muscle cell proliferation is modulated by the growth amplification factors serotonin and adenosine diphosphate. Circulation 90, 1908–1918 10.1161/01.CIR.90.4.1908
    1. Pakala R., Willerson J.T. and Benedict C.R. (1994) Mitogenic effect of serotonin on vascular endothelial cells. Circulation 90, 1919–1926 10.1161/01.CIR.90.4.1919
    1. Hisano N., Yatomi Y., Satoh K., Akimoto S., Mitsumata M., Fujino M.A.. et al. (1999) Induction and suppression of endothelial cell apoptosis by sphingolipids: a possible in vitro model for cell-cell interactions between platelets and endothelial cells. Blood 93, 4293–4299
    1. Lee K.S., Wilson J.J., Rabago D.P., Baer G.S., Jacobson J.A. and Borrero C.G. (2011) Musculoskeletal applications of platelet-rich plasma: fad or future? AJR Am. J. Roentgenol. 196, 628–636 10.2214/AJR.10.5975
    1. Mause S.F., Ritzel E., Liehn E.A., Hristov M., Bidzhekov K., Müller-Newen G.. et al. (2010) Platelet microparticles enhance the vasoregenerative potential of angiogenic early outgrowth cells after vascular injury. Circulation 122, 495–506 10.1161/CIRCULATIONAHA.109.909473
    1. Stellos K., Langer H., Daub K.. et al. (2008) Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells. Circulation 117, 206–215 10.1161/CIRCULATIONAHA.107.714691
    1. Stellos K., Bigalke B., Langer H.. et al. (2009) Expression of stromal-cell-derived factor-1 on circulating platelets is increased in patients with acute coronary syndrome and correlates with the number of CD34+ progenitor cells. Eur. Heart J. 30, 584–593 10.1093/eurheartj/ehn566
    1. Geisler T., Fekecs L., Wurster T.. et al. (2012) Association of platelet-SDF-1 with hemodynamic function and infarct size using cardiac MR in patients with AMI. Eur. J. Radiol. 81, e486–e490 10.1016/j.ejrad.2011.06.019
    1. Stellos K., Bigalke B., Borst O.. et al. (2013) Circulating platelet-progenitor cell coaggregate formation is increased in patients with acute coronary syndromes and augments recruitment of CD34+ cells in the ischaemic microcirculation. Eur. Heart J. 34, 2548–2556 10.1093/eurheartj/eht131
    1. Daub K., Langer H., Seizer P.. et al. (2006) Platelets induce differentiation of human CD34+ progenitor cells into foam cells and endothelial cells. FASEB J. 20, 2559–2561 10.1096/fj.06-6265fje
    1. Hu X., Wang C. and Rui Y. (2012) An experimental study on effect of autologous platelet-rich plasma on treatment of early intervertebral disc degeneration. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 26, 977–983
    1. Fabi S. and Sundaram H. (2014) The potential of topical and injectable growth factors and cytokines for skin rejuvenation. Facial Plast. Surg. 30, 157–171 10.1055/s-0034-1372423
    1. Babu M. and Wells A. (2001) Dermal-epidermal communication in wound healing. Wounds 13, 183–189
    1. Müller R., Bravo R., Burckhardt J. and Curran T. (1984) Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 312, 716–720 10.1038/312716a0
    1. Pardee A.B. (1989) G1 events and regulation of cell proliferation. Science 246, 603–608 10.1126/science.2683075
    1. Larson R.C., Ignotz G.G. and Currie W.B. (1992) Platelet derived growth factor (PDGF) stimulates development of bovine embryos during the fourth cell cycle. Development 115, 821–826
    1. Lauffenburger D.A. and Horwitz A.F. (1996) Cell migration. Cell 84, 359–369 10.1016/S0092-8674(00)81280-5
    1. Wu Y.C. and Horvitz H.R. (1998) C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 392, 501–504 10.1038/33163
    1. Duchek P., Somogyi K., Jékely G., Beccari S. and Rørth P. (2001) Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell 107, 17–26 10.1016/S0092-8674(01)00502-5
    1. Montell D.J., Rørth P. and Spradling A.C. (1992) Slow border cells, a locus required for a developmentally regulated cell migration during oogenesis, encodes Drosophila C/EBP. Cell 71, 51–62 10.1016/0092-8674(92)90265-E
    1. Pantos K., Nitsos N., Kokkali G., Vaxevanoglu T., Markomichaki C., Pantou A.. et al. (2016) Ovarian rejuvenation and folliculogenesis reactivation in peri-menopausal women after autologous platelet-rich plasma treatment. Abstracts, ESHRE 32nd Annual Meeting, Helsinki, Finland, 3–6 July 2016. Hum. Reprod. i301
    1. Bonilla Horcajo C., Zurita Castillo M. and Vaquero Crespo J. (2018) Platelet-rich plasma-derived scaffolds increase the benefit of delayed mesenchymal stromal cell therapy after severe traumatic brain injury. Cytotherapy 20, 314–321 10.1016/j.jcyt.2017.11.012
    1. Sánchez M., Delgado D., Pompei O., Pérez J.C., Sánchez P., Garate A.. et al. (2018) Treating severe knee osteoarthritis with combination of intra-osseous and intra-articular infiltrations of platelet-rich plasma: an observational study. Cartilage 1947603518756462
    1. Tawfik A.A. and Osman M.A.R. (2018) The effect of autologous activated platelet-rich plasma injection on female pattern hair loss: a randomized placebo-controlled study. J. Cosmet. Dermatol. 17, 47–53 10.1111/jocd.12357
    1. Gurtner G.C., Werner S., Barrandon Y. and Longaker M.T. (2008) Wound repair and regeneration. Nature 453, 314–321 10.1038/nature07039
    1. Stellos K., Kopf S., Paul A., Marquardt J.U., Gawaz M., Huard J.. et al. (2010) Platelets in regeneration. Semin. Thromb. Hemost. 36, 175–184 10.1055/s-0030-1251502
    1. Sills E.S., Rickers N.S., Li X. and Palermo G.D. (2018) First data on in vitro fertilization and blastocyst formation after intraovarian injection of calcium gluconate-activated autologous platelet rich plasma. Gynecol. Endocrinol. 1–5
    1. Sfakianoudis K., Simopoulou M., Nitsos N., Rapani A., Pantou A., Vaxevanoglou T.. et al. (2018) A case series on platelet-rich plasma revolutionary management of poor responder patients. Gynecol. Obstet. Invest. 1–8
    1. Rinder H.M., Bonan J.M., Ault K.A. and Smith B.R. (1991) Activated and unactivated platelet adhesion to monocytes and neutrophils. Blood 78, 1760–1769
    1. Waselau M., Sutter W.W., Genovese R.L. and Bertone A.L. (2008) Intralesional injection of platelet-rich plasma followed by controlled exercise for treatment of midbody suspensory ligament desmitis in standardbred racehorses. J. Am. Vet. Med. Assoc. 232, 1515–1520 10.2460/javma.232.10.1515
    1. Fufa D., Shealy B., Jacobson M., Sherwin K. and Murray M.M. (2008) Activation of platelet-rich plasma using Type I collagen. J. Oral Maxillofac. Surg. 66, 684–690 10.1016/j.joms.2007.06.635
    1. Vos R.J., Weir A., van Schie H.T.M., Bierma-Zeinstra S.M.A., Verhaar J.A.N., Weinans H.. et al. (2010) Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial. JAMA 303, 144–149 10.1001/jama.2009.1986
    1. Kitoh H., Kitakoji T., Tsuchiya H., Mitsuyama H., Nakamura H., Katoh M.. et al. (2004) Transplantation of marrow-derived mesenchymal stem cell and platelet-rich plasma during distraction osteogenesis: a preliminary result of three cases. Bone 35, 892–898 10.1016/j.bone.2004.06.013
    1. Everts P.A.M., Mahoney C.B., Hoffmann J.J.M.L., Schönberger J.P., Box H.A.M., Van Zundert A.. et al. (2006) Platelet-rich plasma preparation using three devices: implications for platelet activation and platelet growth factor release. Growth Factors 24, 165–171 10.1080/08977190600821327
    1. Gandhi A., Doumas C., O’Connor J.P., Parsons J.R. and Lin S.S. (2006) The effects of local platelet rich plasma delivery on diabetic fracture healing. Bone 38, 540–546 10.1016/j.bone.2005.10.019
    1. Virchenko O. and Aspenberg P. (2006) How one platelet injection after tendon injury can lead to a stronger tendon after 4 weeks. Acta Orthop. 77, 806–812 10.1080/17453670610013033
    1. Monteiro S.O., Lepage O.M. and Theoret C.L. (2009) Effects of platelet-rich plasma on the repair of wounds on the distal aspect of the forelimb in horses. Am. J. Vet. Res. 70, 277–282 10.2460/ajvr.70.2.277
    1. Zandim B.M., de Souza M.V., Magalhães P.C., Benjamin L., Maia L., de Oliveira A.C.. et al. (2012) Platelet activation: Ultrastructure and morphometry in platelet-rich plasma of horses. Pesq. Vet. Bras. 32, 83–92 10.1590/S0100-736X2012000100014
    1. Hanna C.B. and Hennebold J.D. (2014) Ovarian germline stem cells: an unlimited source of oocytes? Fertil. Steril. 101, 20–30 10.1016/j.fertnstert.2013.11.009
    1. Dunlop C.E. and Telfer E.E. (2013) Anderson RA Ovarian stem cells—potential roles in infertility treatment and fertility preservation. Maturitas 76, 279–283 10.1016/j.maturitas.2013.04.017
    1. Yuan J., Zhang D., Wang L., Liu M., Mao J., Yin Y.. et al. (2013) No evidence for neo-oogenesis may link to ovarian senescence in adult monkey. Stem Cells 31, 2538–2550 10.1002/stem.1480
    1. Lei L. and Spradling A.C. (2013) Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles. Proc. Nat. Acad. Sci. U.S.A. 110, 8585–9690 10.1073/pnas.1306189110
    1. Lee S.T., Gong S.P., Yum K.E., Lee E.J., Lee C.H., Choi J.H.. et al. (2013) Transformation of somatic cells into stem cell-like cells under a stromal niche. FASEB J. 27, 2644–2856 10.1096/fj.12-223065
    1. Betsholtz C., Karlsson L. and Lindahl P. (2001) Developmental roles of platelet-derived growth factors. Bioessays 23, 494–507 10.1002/bies.1069
    1. Powell K. (2012) Egg-making stem cells found in adult ovaries. Nature 483, 16 10.1038/483016a
    1. Sills E.S., Li X., Rickers N.S., Wood S.H. and Palermo G.D. (2019) Metabolic and neurobehavioral response following intraovarian administration of autologous activated platelet rich plasma: first qualitative data. Neuroendocrinol. Lett. 39, 427–433
    1. Sills E.S., Rickers N.S., Svid C.S., Rickers J.M. and Wood S.H. (2019) Normalized ploidy following 20 consecutive blastocysts with chromosomal error: healthy 46,XY pregnancy with IVF after intraovarian injection of autologous enriched platelet-derived growth factors. Int. J. Mol. Cell. Med. 8(1): in press

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe