There have been studies on role of

There have been studies on role of endothelin 1 in pathogenesis of TAO [60]. It is shown that patients with TAO have elevated serum levels of endothelin 1. In a study by De Haro et al. 13 patients received oral endothelin antagonist bosentan at dose 65 mg twice daily for a month followed by 125 mg twice daily. It was seen that though patients continued to smoke, an overall 92% of patients showed clinical improvement with only 2 patients requiring minor amputations. Ten out of twelve patients showed an increase in distal blood flow demonstrated by digital angiography. Bosentan treatment may result in an improvement of clinical, angiographic, and endothelial function outcomes. Bosentan should be investigated further in the management of TAO patients [61].

There have been studies reporting use of gene transfer to induce therapeutic angiogenesis in TAO. Isner et al. [62] showed encouraging results in patients receiving intramuscular injections of vascular endothelial growth factor (VEGF). In a study by Kim et al. [63] he evaluated the safety of intramuscular VEGF gene transfer, using naked plasmid DNA in seven patients with TAO. The injections were well tolerated. Ischaemic ulcers healed or improved in four of six patients. Five of seven patients showed an increase in collateral vessels around the injection sites.

Endothelial progenitor cells (EPCs) belong to an immature cell population that is capable of differentiating into mature endothelial cells. In adults, EPCs mainly reside in bone marrow (BM) and are more proliferative and migrative than terminally differentiated endothelial cells. EPCs can be clinically isolated as CD34þ or AC133þ mononuclear cells (MNCs) from adult BM or peripheral blood (PB) [64]. Tissue ischemia or systemic administration of G-CSF, GM-CSF, vascular endothelial growth factor, or estrogen enhances mobilization of EPCs from BM into PB, and the mobilized EPCs specifically home to sites of nascent neovascularization, thereby contributing to vascular repair.

Many studies have shown efficiency of autologous bone marrow cell injections into ischemic limbs [65]. In recent times, there is a trend towards usage of peripheral blood stem cells as alternate to BM stem cells. In a study by Moriya et al. [66] in 42 patients of TAO treated with peripheral blood mononuclear stem cells, improvement of ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of major amputation was decreased markedly by treatment.

In a study by Kawamoto et al. [67] in 17 patients with TAO who were treated with intramuscular injection of G CSF mobilized CD34+ cells from peripheral blood. During the 12-week observation after cell therapy, the Wong-Baker FACES pain rating scale, transcutaneous partial oxygen pressure, total or pain-free walking distance, and ulcer size serially improved in all patients.

Cell therapies using bone marrow mononuclear cells (BM-MNCs) and peripheral blood mononuclear cells (PBMNCs) have effective outcomes in patients with peripheral artery disease and TAO. The adipose tissue is abundant in the human body and is consistently replenished. Therefore, this tissue is an ideal source of MSCs. It has been shown that adipose tissue derived MSCs (ATMSCs) have characteristics similar to those of bone marrow stromal cells (BMSCs) [68]. ATMSCs differentiate into endothelial cells and have a proangiogenic effect. In a study by Lee et al. [69] 15 patients with TAO were treated with intramuscular injections of ATMSCs; it was seen that clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during followup, and all amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSCs implantation showed formation of numerous vascular collateral networks across affected arteries. Further large-scale randomized trials are required to assess the long-term benefits of stem cell therapy.

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Ada studi peran endotelin 1 dalam patogenesis Tao [60]. Itu ditunjukkan bahwa pasien dengan TAO mengalami peningkatan kadar serum endotelin 1. Dalam sebuah studi oleh De Haro et al. 13 pasien menerima oral endotelin antagonis bosentan dosis 65 mg dua kali sehari selama satu bulan yang diikuti oleh 125 mg dua kali sehari. Ianya dilihat bahwa meskipun pasien terus asap, keseluruhan 92% dari pasien menunjukkan peningkatan klinis dengan pasien hanya 2 yang memerlukan amputasi kecil. Sepuluh dari dua belas pasien menunjukkan peningkatan aliran darah distal ditunjukkan oleh digital angiografi. Bosentan pengobatan dapat mengakibatkan perbaikan hasil klinis, angiographic, dan endotel fungsi. Bosentan harus diselidiki lebih lanjut dalam pengelolaan pasien TAO [61].Ada studi yang melaporkan penggunaan transfer gen untuk menginduksi terapeutik angiogenesis di TAO. Isner et al. [62] menunjukkan hasil menggembirakan pada pasien yang mendapat suntikan intraotot faktor pertumbuhan endotel vaskular (VEGF). Dalam sebuah studi oleh Kim et al. [63] Ia dievaluasi keselamatan intramuskular transfer gen VEGF, menggunakan DNA telanjang plasmid pada tujuh orang pasien dengan TAO. Suntikan yang ditoleransi dengan baik. Iskemik maag sembuh atau ditingkatkan dalam empat dari enam pasien. Lima dari tujuh pasien menunjukkan peningkatan agunan pembuluh di sekitar situs injeksi.Sel-sel endotel leluhur (EPCs) milik populasi sel dewasa yang mampu membedakan ke sel-sel endotel yang matang. Pada orang dewasa, EPCs terutama tinggal di sumsum tulang (BM) dan lebih proliferatif dan migrative daripada parah dibedakan sel-sel endotel. EPCs dapat klinis terisolasi sebagai CD34þ atau AC133þ perlengketan sel (MNCs) dari BM dewasa atau darah perifer (PB) [64]. Iskemia jaringan atau administrasi sistemik dalam G-CSF, GM-CSF, faktor pertumbuhan endotel vaskular atau estrogen meningkatkan mobilisasi EPCs dari BM ke dalam PB, dan EPCs yang dimobilisasi secara khusus rumah ke situs Choroidal baru lahir, sehingga memberikan kontribusi bagi perbaikan pembuluh darah.Banyak penelitian telah menunjukkan efisiensi autologous sumsum tulang sel suntikan ke tungkai iskemik [65]. Dalam beberapa kali, ada kecenderungan ke arah penggunaan sel induk darah perifer sebagai alternatif untuk sel-sel induk BM. Dalam sebuah studi oleh Moriya et al. [66] pada 42 pasien diobati dengan sel-sel induk darah perifer perlengketan Tao, perbaikan gejala iskemik diamati di 60% sampai 70% pasien. Tingkat tahunan utama amputasi menurun tajam dengan pengobatan.Dalam sebuah studi oleh Kawamoto et al. [67] pada 17 pasien dengan TAO yang diperlakukan dengan injeksi intramuskular dari G CSF dimobilisasi CD34 + sel-sel dari darah perifer. Selama 12 minggu pengamatan setelah terapi sel, Wong-Baker wajah nyeri skala rating, transcutaneous oksigen parsial tekanan, total atau bebas rasa sakit berjalan kaki, dan ulkus ukuran serial meningkat pada semua pasien.Cell therapies using bone marrow mononuclear cells (BM-MNCs) and peripheral blood mononuclear cells (PBMNCs) have effective outcomes in patients with peripheral artery disease and TAO. The adipose tissue is abundant in the human body and is consistently replenished. Therefore, this tissue is an ideal source of MSCs. It has been shown that adipose tissue derived MSCs (ATMSCs) have characteristics similar to those of bone marrow stromal cells (BMSCs) [68]. ATMSCs differentiate into endothelial cells and have a proangiogenic effect. In a study by Lee et al. [69] 15 patients with TAO were treated with intramuscular injections of ATMSCs; it was seen that clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during followup, and all amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSCs implantation showed formation of numerous vascular collateral networks across affected arteries. Further large-scale randomized trials are required to assess the long-term benefits of stem cell therapy.