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Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases.

Bukovsky A - Reprod. Biol. Endocrinol. (2015)

Bottom Line: Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells.If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions.Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. a_buko@comcast.net.

ABSTRACT
In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

No MeSH data available.


Related in: MedlinePlus

In vitrodeveloping oocytes are supplied with meiotically nonfunctional organelles from fibroblasts or satellite cells. Time lapse photography shows that early developing oocytes (o, panel A) are low in optically dense cytoplasmic organelles (white open arrow). They can be joined (arrowhead) by fibroblast-like cells (fb), providing additional organelles. Such fibroblast-type cells initially show optically dense organelles close to the nucleus (black solid arrow), but not in the arm extended toward the oocyte (white solid arrow). Within 10 min (panel B), however, the optically dense organelles are apparent in the extended arm (solid black arrow) and within adjacent oocyte cytoplasm (black arrowhead) and distant oocyte regions (black open arrow). At 4h 25 min (panel C), however, the fibro-oocyte (fbo) hybrid is formed and regressing oocyte (ro) exhibits depletion of organelles (arrow) accumulated by the fibroblast (arrowhead). Alternatively, the developing oocytes (o, panel D) deficient in cytoplasmic organelles (white arrow) exploit the satellite cells (s), which are produced by the oocytes themselves. The oocyte is supplied by suicidal satellite cell by a tube like ring canal - (black arrowhead; see inset). In panel E the oocyte exhibits enhanced content of the optically dense organelles (black arrow) and the ring canal draining the satellite disappears (white arrowhead - see inset). The satellite cell size is reduced (dashed line) and the perinuclear space is altered (compare with panel D). Oocytes enriched by satellites’ organelles (panel F) exhibit good morphology [200 micron size, germinal vesicle (gv), and thick zona pellucida (zp)], but are unable to resume meiosis II due to the lack of meiotically functional organelles provided by secondary Balbiani body derived from granulosa cells in vivo. Bar in A for A-E. Panel C reprinted from Ref. [26]: © Antonin Bukovsky. Other panels adapted from Ref. [34], with a permission: © Wiley-Liss, Inc.
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Fig6: In vitrodeveloping oocytes are supplied with meiotically nonfunctional organelles from fibroblasts or satellite cells. Time lapse photography shows that early developing oocytes (o, panel A) are low in optically dense cytoplasmic organelles (white open arrow). They can be joined (arrowhead) by fibroblast-like cells (fb), providing additional organelles. Such fibroblast-type cells initially show optically dense organelles close to the nucleus (black solid arrow), but not in the arm extended toward the oocyte (white solid arrow). Within 10 min (panel B), however, the optically dense organelles are apparent in the extended arm (solid black arrow) and within adjacent oocyte cytoplasm (black arrowhead) and distant oocyte regions (black open arrow). At 4h 25 min (panel C), however, the fibro-oocyte (fbo) hybrid is formed and regressing oocyte (ro) exhibits depletion of organelles (arrow) accumulated by the fibroblast (arrowhead). Alternatively, the developing oocytes (o, panel D) deficient in cytoplasmic organelles (white arrow) exploit the satellite cells (s), which are produced by the oocytes themselves. The oocyte is supplied by suicidal satellite cell by a tube like ring canal - (black arrowhead; see inset). In panel E the oocyte exhibits enhanced content of the optically dense organelles (black arrow) and the ring canal draining the satellite disappears (white arrowhead - see inset). The satellite cell size is reduced (dashed line) and the perinuclear space is altered (compare with panel D). Oocytes enriched by satellites’ organelles (panel F) exhibit good morphology [200 micron size, germinal vesicle (gv), and thick zona pellucida (zp)], but are unable to resume meiosis II due to the lack of meiotically functional organelles provided by secondary Balbiani body derived from granulosa cells in vivo. Bar in A for A-E. Panel C reprinted from Ref. [26]: © Antonin Bukovsky. Other panels adapted from Ref. [34], with a permission: © Wiley-Liss, Inc.

Mentions: Oocyte like cells developed in OSC cultures are very immature, since they do not exhibit ZP3 expression and CK positive Balbiani bodies. Observations from time lapse photography [34] (Figure 6) have shown that early developing oocytes have few optically dense cytoplasmic organelles. They appear to be smart and join fibroblast-type cells which provide additional organelles. Such fibroblast-type cells initially show optically dense organelles close to the nucleus, but not in the arm extended toward the oocyte. Within 10 min from the previous photograph, however, optically dense organelles are evidenced in the extended fibroblast arm, within adjacent oocyte cytoplasm, and also in distant oocyte regions. After 4 h and 25 min, however, the fibro-oocyte hybrid is formed and the dominant fibroblast cell collects organelles from regressing oocyte.Figure 6


Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases.

Bukovsky A - Reprod. Biol. Endocrinol. (2015)

In vitrodeveloping oocytes are supplied with meiotically nonfunctional organelles from fibroblasts or satellite cells. Time lapse photography shows that early developing oocytes (o, panel A) are low in optically dense cytoplasmic organelles (white open arrow). They can be joined (arrowhead) by fibroblast-like cells (fb), providing additional organelles. Such fibroblast-type cells initially show optically dense organelles close to the nucleus (black solid arrow), but not in the arm extended toward the oocyte (white solid arrow). Within 10 min (panel B), however, the optically dense organelles are apparent in the extended arm (solid black arrow) and within adjacent oocyte cytoplasm (black arrowhead) and distant oocyte regions (black open arrow). At 4h 25 min (panel C), however, the fibro-oocyte (fbo) hybrid is formed and regressing oocyte (ro) exhibits depletion of organelles (arrow) accumulated by the fibroblast (arrowhead). Alternatively, the developing oocytes (o, panel D) deficient in cytoplasmic organelles (white arrow) exploit the satellite cells (s), which are produced by the oocytes themselves. The oocyte is supplied by suicidal satellite cell by a tube like ring canal - (black arrowhead; see inset). In panel E the oocyte exhibits enhanced content of the optically dense organelles (black arrow) and the ring canal draining the satellite disappears (white arrowhead - see inset). The satellite cell size is reduced (dashed line) and the perinuclear space is altered (compare with panel D). Oocytes enriched by satellites’ organelles (panel F) exhibit good morphology [200 micron size, germinal vesicle (gv), and thick zona pellucida (zp)], but are unable to resume meiosis II due to the lack of meiotically functional organelles provided by secondary Balbiani body derived from granulosa cells in vivo. Bar in A for A-E. Panel C reprinted from Ref. [26]: © Antonin Bukovsky. Other panels adapted from Ref. [34], with a permission: © Wiley-Liss, Inc.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4414002&req=5

Fig6: In vitrodeveloping oocytes are supplied with meiotically nonfunctional organelles from fibroblasts or satellite cells. Time lapse photography shows that early developing oocytes (o, panel A) are low in optically dense cytoplasmic organelles (white open arrow). They can be joined (arrowhead) by fibroblast-like cells (fb), providing additional organelles. Such fibroblast-type cells initially show optically dense organelles close to the nucleus (black solid arrow), but not in the arm extended toward the oocyte (white solid arrow). Within 10 min (panel B), however, the optically dense organelles are apparent in the extended arm (solid black arrow) and within adjacent oocyte cytoplasm (black arrowhead) and distant oocyte regions (black open arrow). At 4h 25 min (panel C), however, the fibro-oocyte (fbo) hybrid is formed and regressing oocyte (ro) exhibits depletion of organelles (arrow) accumulated by the fibroblast (arrowhead). Alternatively, the developing oocytes (o, panel D) deficient in cytoplasmic organelles (white arrow) exploit the satellite cells (s), which are produced by the oocytes themselves. The oocyte is supplied by suicidal satellite cell by a tube like ring canal - (black arrowhead; see inset). In panel E the oocyte exhibits enhanced content of the optically dense organelles (black arrow) and the ring canal draining the satellite disappears (white arrowhead - see inset). The satellite cell size is reduced (dashed line) and the perinuclear space is altered (compare with panel D). Oocytes enriched by satellites’ organelles (panel F) exhibit good morphology [200 micron size, germinal vesicle (gv), and thick zona pellucida (zp)], but are unable to resume meiosis II due to the lack of meiotically functional organelles provided by secondary Balbiani body derived from granulosa cells in vivo. Bar in A for A-E. Panel C reprinted from Ref. [26]: © Antonin Bukovsky. Other panels adapted from Ref. [34], with a permission: © Wiley-Liss, Inc.
Mentions: Oocyte like cells developed in OSC cultures are very immature, since they do not exhibit ZP3 expression and CK positive Balbiani bodies. Observations from time lapse photography [34] (Figure 6) have shown that early developing oocytes have few optically dense cytoplasmic organelles. They appear to be smart and join fibroblast-type cells which provide additional organelles. Such fibroblast-type cells initially show optically dense organelles close to the nucleus, but not in the arm extended toward the oocyte. Within 10 min from the previous photograph, however, optically dense organelles are evidenced in the extended fibroblast arm, within adjacent oocyte cytoplasm, and also in distant oocyte regions. After 4 h and 25 min, however, the fibro-oocyte hybrid is formed and the dominant fibroblast cell collects organelles from regressing oocyte.Figure 6

Bottom Line: Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells.If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions.Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. a_buko@comcast.net.

ABSTRACT
In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.

No MeSH data available.


Related in: MedlinePlus