**3. Conclusion**

Since the retrograde implantation theory developed in the 1920s by Sympson, the etiology of endometriosis involves a complex interplay of genetic, immunologic, inflammatory and environmental factors. Nevertheless, endometriosis remains an enigmatic disease to cause pelvic pain and infertility. The characteristics of recurrence and wide spray make the disease malignant-like. Stem cell theory opens the latest advanced avenue for etiology of endometriosis. Increasing studies illustrate the presence of endometrial stem/progenitor cells, either from the residing cells in the endometrium or reprogram of bone marrow MSC. EPC from the bone marrow can contribute to the de novo angiogenesis. The EPC enhances endometriosis formation. Endometriosis is a recurrent disease, thus making the treatment costly and psychologically debilitating. Novel treatment modalities include selective ER modulators, tissue factor (the initiator of the hemostatic cascade) targets, statins and angiogenic blockers, immunoconjugate molecule and stem cells. Administration of endometrial stem cells to the disease model could suppress the immunological reaction, and was supposed to have potential in the treatment. Other therapy modalities to target the stem cells flux, adhesion and signalling control pathway are novel treatment strategies.

### **4. Acknowledgment**

The author thanks sincerely to Dr. Yu-Chih Wang for his edition.

#### **5. References**

272 Endometriosis - Basic Concepts and Current Research Trends

Biomarker Relevance/function Expression Oct-4 Stem cell Positive hTERT Telomerase reverse transcriptase Positive CD9 MSC/angiogenesis Positive CD29 MSC/adhesion molecule Positive CD41a MSC/fibrinogen receptor Positive CD44 MSC/hyaluronic acid receptor Positive CD73 MSC/migration Positive CD90 MSC/marker of T cells, hematopoietic and MSC Positive CD105 MSC Positive CD49f MSC Positive Musashi-1 Endometrial stem cell Positive CD34 Hematopoietic stem cell Negative CD45 Leukocyte cell Negative SSEA-4 Embryonic stem cell Negative Nanog Embryonic stem cell Negative

MSC: mesenchymal stem cell Modified from Meng et al., 2007

**3. Conclusion** 

Table 1. Biomarkers of endometrial mesenchymal stem cells.

Since the retrograde implantation theory developed in the 1920s by Sympson, the etiology of endometriosis involves a complex interplay of genetic, immunologic, inflammatory and environmental factors. Nevertheless, endometriosis remains an enigmatic disease to cause pelvic pain and infertility. The characteristics of recurrence and wide spray make the disease malignant-like. Stem cell theory opens the latest advanced avenue for etiology of endometriosis. Increasing studies illustrate the presence of endometrial stem/progenitor cells, either from the residing cells in the endometrium or reprogram of bone marrow MSC. EPC from the bone marrow can contribute to the de novo angiogenesis. The EPC enhances endometriosis formation. Endometriosis is a recurrent disease, thus making the treatment costly and psychologically debilitating. Novel treatment modalities include selective ER modulators, tissue factor (the initiator of the hemostatic cascade) targets, statins and angiogenic blockers, immunoconjugate molecule and stem cells. Administration of endometrial stem cells to the disease model could suppress the immunological reaction, and was supposed to have potential in the treatment. Other therapy modalities to target the stem

cells flux, adhesion and signalling control pathway are novel treatment strategies.


Stem Cell as the Novel Pathogenesis of Endometriosis 275

Maruyama T.; Masuda H.; Ono M.; Kajitani T. & Yoshimura Y. (2010). Human uterine

Masuda H.; Maruyama T.; Hiratsu E.; Yamane J.; Iwanami A.; Nagashima T.; Ono M.;

Meng X.; Ichim T. E.; Zhong J.; Rogers A.;, Yin Z.; Jackson J.; Wang H.; Ge W.; Bogin V.;

Mints M.; Jansson M.; Sadeghi B.; Westgren M.; Uzunel M.; Hassan M. & Palmblad J. (2008).

Musina R. A.; Belyavski A. V.; Tarusova O. V.; Solovyova E. V. & Sukhikh G. T. (2008).

Pacchiarotti A.; Caserta D.; Sbracia M. & Moscarini M. (2011). Expression of oct-4 and c-kit

Schwab K. E. & Gargett C. E. (2007). Co-expression of two perivascular cell markers isolates

Taylor H. S. (2004). Endometrial cells derived from donor stem cells in bone marrow

Taylor H. S.; Osteen K. G.; Bruner-Tran K. L.; Krikun G.; Sokalska A. & Duleba A. J. (2011).

Traynor A. E.; Barr W. G.; Rosa R. M.; Rodriguez J.; Oyama Y.; Baker S.; Brush M. & Burt R.

Wolff E. F.; Wolff A. B.; Hongling D. & Taylor H. S. (2007). Demonstration of multipotent

Wolff E. F.; Gao X. B.; Yao K. V.; Andrews Z. B.; Du H.; Elsworth J. D. & Taylor H. S. (2011).

22, No. 11, (November 2007), pp. 2903-2911, ISSN 0268-1161.

*Reproduction,* Vol. 140, No. 1, (July 2010), pp. 11-22, ISSN 1470-1626.

(February 2007), pp. 1925-1930, ISSN 0027-8424.

2007), pp. 57, ISSN 1479-5876.

143, ISSN 0268-1161.

1171-1173, ISSN 0015-0282.

(July 2004), pp. 81-85, ISSN 0098-7484.

(September 2011), pp. 814-823, ISSN 1933-7191.

11, (November), pp. 2917-2923, ISSN 1529-0131.

0007-4888.

7191.

stem/progenitor cells: their possible role in uterine physiology and pathology.

Miyoshi H.; Okano H. J.; Ito M.; Tamaoki N.; Nomura T.; Okano H.; Matsuzaki Y. & Yoshimura Y. (2007). Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/gamma c(null) immunodeficient mice. *The Proceedings of the National Academy of Sciences USA,* Vol. 104, No. 6,

Chan K. W.; Thébaud B. & Riordan N. H. (2007). Endometrial regenerative cells: a novel stem cell population. *Journal of Translational Medicine,* Vol. 5, (November

Endometrial endothelial cells are derived from donor stem cells in a bone marrow transplant recipient. *Human Reproduction,* Vol. 23, No. 1, (January 2008), pp. 139-

Endometrial mesenchymal stem cells isolated from the menstrual blood. *Bulletin of experimental biology and medicine,* Vol. 145, No. 4, (April 2008), pp. 539-543, ISSN

antigens in endometriosis. *Fertility and Sterility,* Vol. 95, No. 3, (March 2011), pp.

mesenchymal stem-like cells from human endometrium. *Human Reproduction,* Vol.

transplant recipients. *Journal of the American Medical Association,* Vol. 292, No. 1,

Novel Therapies Targeting Endometriosis. *Reproductive Sciences,* Vol. 18, No. 9,

K. (2002). Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients. *Arthritis and Rheumatism,* Vol. 46, No.

stem cells in the adult human endometrium by in vitro chondrogenesis. *Reproductive ciences,* Vol. 14No. 6, (September 2007), pp. 524-533, ISSN 1933-

Endometrial stem cell transplantation restores dopamine production in a


http://doi:10. 1016/j. fertnstert. 2011. 06. 041


Juo S. H.; Wang T. N.; Lee J. N.; Wu M. T.; Long C. Y. & Tsai E. M. (2006). CYP17, CYP1A1

Juo S. H.; Wu R.; Lin C. S.; Wu M. T.; Lee J. N. & Tsai E. M. (2009). A functional promoter

Kaitu'u-Lino T. J.; Ye L. & Gargett C. E. (2010). Reepithelialization of the uterine surface

Kao A. P.; Wang K. H.; Chang C. C.; Lee J. N.; Long C. Y.; Chen H. S.; Tsai C. F.; Hsieh T. H.

Kao A. P.; Wang K. H.; Long C. Y.; Chai C. Y.; Tsai C. F.; Hsieh T. H.; Hsu C. Y.; Chang C.

Kim J. Y.; Tavaré S. & Shibata D. (2005). Counting human somatic cell replications:

Kondo W.; Dal Lago E. A.; Francisco J. C.; Simeoni R. B.; de Noronha L.; Martins A. P.; de

Laschke M. W.; Giebels C.; Nickels R. M.; Scheuer C. & Menger M. D. (2011). Endothelial

Lynch L.; Golden-Mason L.; Eogan M.; O'Herlihy C. & O'Farrelly C. (2007). Cells with

ISSN 1460-2350.

ISSN 0013-7227.

Available from

0027-8424.

0002-9440.

1161.

http://doi:10. 1016/j. fertnstert. 2011. 06. 041

*Gynecology and Reproductive Biology* Available from http://dx. doi. org/10. 1016/j. ejogrb. 2011. 05. 004.

0282.

0282.

and COMT polymorphisms and the risk of adenomyosis and endometriosis in Taiwanese women. *Human Reproduction,* Vol. 21, No. 6, (June 2006), pp. 1498-1502,

polymorphism in interleukin-10 gene influences susceptibility to endometriosis. *Fertility and Sterility,* Vol. 92, No. 4, (October 2009), pp. 1228-1233, ISSN 0015-

arises from endometrial glands: evidence from a functional mouse model of breakdown and repair. *Endocrinology,* Vol. 151, No. 7, (July 2010), pp. 3386-3395,

& Tsai E. M. (2011). Comparative study of human eutopic and ectopic endometrial mesenchymal stem cells and the development of an in vivo endometriotic invasion model. *Fertility and Sterility,* Vol. 95, No. 4, (March 2011), pp. 1308-1315, ISSN 0015-

C.; Lee J. N. & Tsai E. M. (2011). Interleukin-1β induces cyclooxygenase-2 expression and promotes the invasive ability of human mesenchymal stem cells derived from ovarian endometrioma. , In 13. 07. 2011, *Fertility and Sterility*

methylation mirrors endometrial stem cell divisions. *The Proceedings of the National Academy of Sciences USA,* Vol. 102, No. 49, (December 2005), pp. 17739-17744, ISSN

Azevedo M. L.; Ferreira C. C.; Maestrelli P.; Olandoski M.; Guarita-Souza L. C. & do Amaral V. F. (2011). Effect of the bone marrow derived-mononuclear stem cells transplantation in the growth, VEGF-R and TNF-alpha expression of endometrial implants in Wistar rats, In 01. 06. 2011, *The European Journal of Obstetrics &* 

Progenitor Cells Contribute to the Vascularization of Endometriotic Lesions. *The American Journal of Pathology,* Vol. 178, No. 1, (January 2011), pp. 442-450, ISSN

haematopoietic stem cell phenotype in adult human endometrium: relevance to infertility? *Human Reproduction,* Vol. 22, No. 4, (April 2007), pp. 919-926, ISSN 0268-


**14** 

 *Hong Kong* 

**Green Tea for Endometriosis** 

*Prince of Wales Hospital, Shatin, New Territories,* 

Gene Chi Wai Man, Hui Xu and Chi Chiu Wang

*Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong,* 

Endometriosis is a common gynaecological disease, defined by the presence of endometrial tissue outside the uterus, causing pain and infertility of women in reproductive age (Galle, 1989). It is estimated that it occurs in 10-15% for women in the reproductive age and more than 30% of all infertile women are affected (Cramer *et al.*, 2002). However, the actual figure on the total prevalence may even be higher, as the disease is often not diagnosed due to heterogenous clinical manifestations. These manifestations include dysmenorrhoea, dyspareunia, dysuria and chronic abdominal or pelvic pain as well as infertility, resulting in a severely limited quality of life (Davis *et al.*, 2003; Milingos *et al.*, 2006; Vercellini *et al.*, 2007). Thus, the aim on treating endometriosis should ideally target the endometriosis itself, i.e. relieves pain, promotes fertility and prevents reocurrence. Unfortunately, there is no current treatment being able to fulfill all these requirements. All conservative treatments, either medical or surgical, are still liable for disease reocurrence, and they do not address the cause and possible side effects brought upon to the disease mechanism and the patient

In this chapter, we will analyze the rationale and limitations of the current therapy of endometriosis. Also, we will discuss on the latest therapies that hold a higher efficacy and sensitivity on treating the disease. Most importantly, we will highlight the effect of green

In the past, the disease was best thought to be treated surgically. And with the advancement of operative laparoscopy, the treatment of endometriosis could be started as soon as it was diagnosis. However, different researches have shown surgical removal of endometriosis can bought upon many complications and chronicity. Likewise, without medical supplements, the patients would have a high chance for disease reocurrence. Hence, there is a great

The type of treatments offer would depend on the extent or stage of the disease, the amount of pain suffered, and fertility wanted (Valle *et al.*, 2003) (Fig. 1). To perform the best therapy would require complete diagnosis and inspections of the lesion to determine the symptoms and staging of the patient's endometriosis (Olive *et al.*, 2001). The choices of present treatments

demand for medical treatments that can induce a suppression of this disease.

include expectant management, medical therapy and surgical treatment (Table 1).

tea on being a potential remedy toward tackling endometriosis.

**1. Introduction** 

outcomes.

**1.1 Current and new treatment** 

Parkinson's disease model. *Journal of cellular and molecular medicine,* Vol. 15, No. 4, (April 2011), pp. 747-755, ISSN 1582-1838.

Zhou Y.; Gan Y. & Taylor H. S. (2011). Cigarette smoke inhibits recruitment of bonemarrow-derived stem cells to the uterus. *Reproductive Toxicology,* Vol. 31, No. 2, (February 2011), pp. 123-127, ISSN 0890-6238.
