Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion

Hideki Miyachi, James W. Reinhardt, Satoru Otsuru, Shuhei Tara, Hidetaka Nakayama, Tai Yi, Yong Ung Lee, Shinka Miyamoto, Toshihiro Shoji, Tadahisa Sugiura, Christopher K. Breuer, Toshiharu Shinoka

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Acute thrombosis is a crucial cause of bioresorbable vascular graft (BVG) failure. Bone marrow-derived mononuclear cell (BM-MNC)-seeded BVGs demonstrated high graft patency, however, the effect of seeded BM-MNCs against thrombosis remains to be elucidated. Thus, we evaluated an antithrombotic effect of BM-MNC-seeding and utilized platelet-depletion mouse models to evaluate the contribution of platelets to acute thrombosis of BVGs. Methods and results: BVGs were composed of poly(glycolic acid) mesh sealed with poly(L-lactideco-ε-caprolactone). BM-MNC-seeded BVGs and unseeded BVGs were implanted to wild type C57BL/6 mice (n = 10/group) as inferior vena cava interposition conduits. To evaluate platelet effect on acute thrombosis, c-Mpl−/− mice and Pf4-Cre+; iDTR mice with decreased platelet number were also implanted with unseeded BVGs (n = 10/group). BVG patency was evaluated at 2, 4, and 8 weeks by ultrasound. BM-MNC-seeded BVGs demonstrated a significantly higher patency rate than unseeded BVGs during the acute phase (2-week, 90% vs 30%, p =.020), and patency rates of these grafts were sustained until week 8. Similar to BM-MNC-seeded BVGs, C-Mpl−/− and Pf4-Cre+; iDTR mice also showed favorable graft patency (2-week, 90% and 80%, respectively) during the acute phase. However, the patency rate of Pf4-Cre+; iDTR mice decreased gradually after DTR treatment as platelet number recovered to baseline. An in vitro study revealed BM-MNC-seeding significantly inhibited platelet adhesion to BVGs compared to unseeded BVGs, (1.75 ± 0.45 vs 8.69 ± 0.68 × 103 platelets/mm2, p <.001). Conclusions: BM-MNC-seeding and the reduction in platelet number prevented BVG thrombosis and improved BVG patency, and those results might be caused by inhibiting platelet adhesion to the BVG.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalInternational Journal of Cardiology
Volume266
DOIs
StatePublished - Sep 1 2018
Externally publishedYes

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Blood Vessels
Thrombosis
Blood Platelets
Bone Marrow
Transplants
Vascular Patency
Platelet Count
glycolic acid
Inferior Vena Cava
Inbred C57BL Mouse

Keywords

  • Anticoagulation
  • Mononuclear cell
  • Patency
  • Platelet
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion. / Miyachi, Hideki; Reinhardt, James W.; Otsuru, Satoru; Tara, Shuhei; Nakayama, Hidetaka; Yi, Tai; Lee, Yong Ung; Miyamoto, Shinka; Shoji, Toshihiro; Sugiura, Tadahisa; Breuer, Christopher K.; Shinoka, Toshiharu.

In: International Journal of Cardiology, Vol. 266, 01.09.2018, p. 61-66.

Research output: Contribution to journalArticle

Miyachi, Hideki ; Reinhardt, James W. ; Otsuru, Satoru ; Tara, Shuhei ; Nakayama, Hidetaka ; Yi, Tai ; Lee, Yong Ung ; Miyamoto, Shinka ; Shoji, Toshihiro ; Sugiura, Tadahisa ; Breuer, Christopher K. ; Shinoka, Toshiharu. / Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion. In: International Journal of Cardiology. 2018 ; Vol. 266. pp. 61-66.
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abstract = "Background: Acute thrombosis is a crucial cause of bioresorbable vascular graft (BVG) failure. Bone marrow-derived mononuclear cell (BM-MNC)-seeded BVGs demonstrated high graft patency, however, the effect of seeded BM-MNCs against thrombosis remains to be elucidated. Thus, we evaluated an antithrombotic effect of BM-MNC-seeding and utilized platelet-depletion mouse models to evaluate the contribution of platelets to acute thrombosis of BVGs. Methods and results: BVGs were composed of poly(glycolic acid) mesh sealed with poly(L-lactideco-ε-caprolactone). BM-MNC-seeded BVGs and unseeded BVGs were implanted to wild type C57BL/6 mice (n = 10/group) as inferior vena cava interposition conduits. To evaluate platelet effect on acute thrombosis, c-Mpl−/− mice and Pf4-Cre+; iDTR mice with decreased platelet number were also implanted with unseeded BVGs (n = 10/group). BVG patency was evaluated at 2, 4, and 8 weeks by ultrasound. BM-MNC-seeded BVGs demonstrated a significantly higher patency rate than unseeded BVGs during the acute phase (2-week, 90{\%} vs 30{\%}, p =.020), and patency rates of these grafts were sustained until week 8. Similar to BM-MNC-seeded BVGs, C-Mpl−/− and Pf4-Cre+; iDTR mice also showed favorable graft patency (2-week, 90{\%} and 80{\%}, respectively) during the acute phase. However, the patency rate of Pf4-Cre+; iDTR mice decreased gradually after DTR treatment as platelet number recovered to baseline. An in vitro study revealed BM-MNC-seeding significantly inhibited platelet adhesion to BVGs compared to unseeded BVGs, (1.75 ± 0.45 vs 8.69 ± 0.68 × 103 platelets/mm2, p <.001). Conclusions: BM-MNC-seeding and the reduction in platelet number prevented BVG thrombosis and improved BVG patency, and those results might be caused by inhibiting platelet adhesion to the BVG.",
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author = "Hideki Miyachi and Reinhardt, {James W.} and Satoru Otsuru and Shuhei Tara and Hidetaka Nakayama and Tai Yi and Lee, {Yong Ung} and Shinka Miyamoto and Toshihiro Shoji and Tadahisa Sugiura and Breuer, {Christopher K.} and Toshiharu Shinoka",
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T1 - Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion

AU - Miyachi, Hideki

AU - Reinhardt, James W.

AU - Otsuru, Satoru

AU - Tara, Shuhei

AU - Nakayama, Hidetaka

AU - Yi, Tai

AU - Lee, Yong Ung

AU - Miyamoto, Shinka

AU - Shoji, Toshihiro

AU - Sugiura, Tadahisa

AU - Breuer, Christopher K.

AU - Shinoka, Toshiharu

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background: Acute thrombosis is a crucial cause of bioresorbable vascular graft (BVG) failure. Bone marrow-derived mononuclear cell (BM-MNC)-seeded BVGs demonstrated high graft patency, however, the effect of seeded BM-MNCs against thrombosis remains to be elucidated. Thus, we evaluated an antithrombotic effect of BM-MNC-seeding and utilized platelet-depletion mouse models to evaluate the contribution of platelets to acute thrombosis of BVGs. Methods and results: BVGs were composed of poly(glycolic acid) mesh sealed with poly(L-lactideco-ε-caprolactone). BM-MNC-seeded BVGs and unseeded BVGs were implanted to wild type C57BL/6 mice (n = 10/group) as inferior vena cava interposition conduits. To evaluate platelet effect on acute thrombosis, c-Mpl−/− mice and Pf4-Cre+; iDTR mice with decreased platelet number were also implanted with unseeded BVGs (n = 10/group). BVG patency was evaluated at 2, 4, and 8 weeks by ultrasound. BM-MNC-seeded BVGs demonstrated a significantly higher patency rate than unseeded BVGs during the acute phase (2-week, 90% vs 30%, p =.020), and patency rates of these grafts were sustained until week 8. Similar to BM-MNC-seeded BVGs, C-Mpl−/− and Pf4-Cre+; iDTR mice also showed favorable graft patency (2-week, 90% and 80%, respectively) during the acute phase. However, the patency rate of Pf4-Cre+; iDTR mice decreased gradually after DTR treatment as platelet number recovered to baseline. An in vitro study revealed BM-MNC-seeding significantly inhibited platelet adhesion to BVGs compared to unseeded BVGs, (1.75 ± 0.45 vs 8.69 ± 0.68 × 103 platelets/mm2, p <.001). Conclusions: BM-MNC-seeding and the reduction in platelet number prevented BVG thrombosis and improved BVG patency, and those results might be caused by inhibiting platelet adhesion to the BVG.

AB - Background: Acute thrombosis is a crucial cause of bioresorbable vascular graft (BVG) failure. Bone marrow-derived mononuclear cell (BM-MNC)-seeded BVGs demonstrated high graft patency, however, the effect of seeded BM-MNCs against thrombosis remains to be elucidated. Thus, we evaluated an antithrombotic effect of BM-MNC-seeding and utilized platelet-depletion mouse models to evaluate the contribution of platelets to acute thrombosis of BVGs. Methods and results: BVGs were composed of poly(glycolic acid) mesh sealed with poly(L-lactideco-ε-caprolactone). BM-MNC-seeded BVGs and unseeded BVGs were implanted to wild type C57BL/6 mice (n = 10/group) as inferior vena cava interposition conduits. To evaluate platelet effect on acute thrombosis, c-Mpl−/− mice and Pf4-Cre+; iDTR mice with decreased platelet number were also implanted with unseeded BVGs (n = 10/group). BVG patency was evaluated at 2, 4, and 8 weeks by ultrasound. BM-MNC-seeded BVGs demonstrated a significantly higher patency rate than unseeded BVGs during the acute phase (2-week, 90% vs 30%, p =.020), and patency rates of these grafts were sustained until week 8. Similar to BM-MNC-seeded BVGs, C-Mpl−/− and Pf4-Cre+; iDTR mice also showed favorable graft patency (2-week, 90% and 80%, respectively) during the acute phase. However, the patency rate of Pf4-Cre+; iDTR mice decreased gradually after DTR treatment as platelet number recovered to baseline. An in vitro study revealed BM-MNC-seeding significantly inhibited platelet adhesion to BVGs compared to unseeded BVGs, (1.75 ± 0.45 vs 8.69 ± 0.68 × 103 platelets/mm2, p <.001). Conclusions: BM-MNC-seeding and the reduction in platelet number prevented BVG thrombosis and improved BVG patency, and those results might be caused by inhibiting platelet adhesion to the BVG.

KW - Anticoagulation

KW - Mononuclear cell

KW - Patency

KW - Platelet

KW - Thrombosis

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