Effect of adenoviral-mediated transfer of transforming growth factor-β1 on colonic anastomotic healing

John Migaly, Jonathan Lieberman, Walter Long, Carol Fisher, Rolando Rolandelli

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

PURPOSE: Transforming growth factor-β1 plays a central role in colonic repair. We examined the temporal effect of vector-mediated transfer of transforming growth factor-β1 on colonic anastomotic healing. METHODS: Male Sprague-Dawley rats (n = 24) underwent transection of the distal colon and single-layer anastomosis. Proximal to the anastomosis, the colon was again transected and a colostomy was matured proximally. The distal colon was intubated with a silicone catheter, tunneled along subcutaneous tissues, and connected to a swivel apparatus for postoperative luminal infusion. Rats were randomized into four groups (n = 6 each). Two control groups received 10 10 plaque-forming units of a Type 5 E1-deleted adenovirus carrying the bacterial β-galactosidase gene either immediately following surgery or on postoperative Day 3. The treatment groups received transforming growth factor-β1 with the same viral construct at parallel time points. On postoperative Day 6, anastomotic bursting pressure and site were determined in situ with the anastomotic tissue subsequently harvested and analyzed by enzyme-linked immunosorbent assay for β-galactosidase and transforming growth factor-β1. RESULTS: When compared with its corresponding control, the group that received the transforming growth factor-β1 gene on postoperative day 3 had a significantly higher bursting pressure (mmHg; 119 ± 16 vs. 160 ± 12, mean ± SD; P = 0.001). While the majority of colons (5/6) from the control group burst at the anastomosis, none of the colons in the group that received transforming growth factor-β1 on day 3 burst at the anastomotic site (P = 0.007). β-Galactosidase levels (pg/ml) in anastomotic tissue were significantly increased in both control groups when compared with their respective treatment groups (101 ± 43 vs. 38 ± 30, P = 0.01 when infused the day of surgery and 243 ± 92 vs. 50 ± 30, P = 0.009 when infused on day 3). Anastomotic levels of transforming growth factor-β1 were also increased in the group receiving the transforming growth factor-β1 gene on day 3 (214 ± 66 vs. 135 ± 24, P = 0.02). CONCLUSIONS: Gene transfer into the healing colonic anastomosis can be effectively achieved via intraluminal administration of adenoviral vectors. Transfer of transforming growth factor-β1 increased the strength of colonic anastomoses when given at Day 3 but not at Day 0, demonstrating its diverse effects in the wound healing sequence. Thus, gene transfer of transforming growth factor-β1 may avoid the need for a diverting stoma in cases of rectal surgery and impaired healing resulting from chemotherapy or radiation.

Original languageEnglish (US)
Pages (from-to)1699-1705
Number of pages7
JournalDiseases of the Colon and Rectum
Volume47
Issue number10
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

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Transforming Growth Factors
Galactosidases
Colon
Control Groups
Genes
Bacterial Genes
Pressure
Colostomy
Subcutaneous Tissue
Silicones
Ambulatory Surgical Procedures
Adenoviridae
Wound Healing
Sprague Dawley Rats
Catheters
Enzyme-Linked Immunosorbent Assay
Radiation
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Migaly, John ; Lieberman, Jonathan ; Long, Walter ; Fisher, Carol ; Rolandelli, Rolando. / Effect of adenoviral-mediated transfer of transforming growth factor-β1 on colonic anastomotic healing. In: Diseases of the Colon and Rectum. 2004 ; Vol. 47, No. 10. pp. 1699-1705.
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abstract = "PURPOSE: Transforming growth factor-β1 plays a central role in colonic repair. We examined the temporal effect of vector-mediated transfer of transforming growth factor-β1 on colonic anastomotic healing. METHODS: Male Sprague-Dawley rats (n = 24) underwent transection of the distal colon and single-layer anastomosis. Proximal to the anastomosis, the colon was again transected and a colostomy was matured proximally. The distal colon was intubated with a silicone catheter, tunneled along subcutaneous tissues, and connected to a swivel apparatus for postoperative luminal infusion. Rats were randomized into four groups (n = 6 each). Two control groups received 10 10 plaque-forming units of a Type 5 E1-deleted adenovirus carrying the bacterial β-galactosidase gene either immediately following surgery or on postoperative Day 3. The treatment groups received transforming growth factor-β1 with the same viral construct at parallel time points. On postoperative Day 6, anastomotic bursting pressure and site were determined in situ with the anastomotic tissue subsequently harvested and analyzed by enzyme-linked immunosorbent assay for β-galactosidase and transforming growth factor-β1. RESULTS: When compared with its corresponding control, the group that received the transforming growth factor-β1 gene on postoperative day 3 had a significantly higher bursting pressure (mmHg; 119 ± 16 vs. 160 ± 12, mean ± SD; P = 0.001). While the majority of colons (5/6) from the control group burst at the anastomosis, none of the colons in the group that received transforming growth factor-β1 on day 3 burst at the anastomotic site (P = 0.007). β-Galactosidase levels (pg/ml) in anastomotic tissue were significantly increased in both control groups when compared with their respective treatment groups (101 ± 43 vs. 38 ± 30, P = 0.01 when infused the day of surgery and 243 ± 92 vs. 50 ± 30, P = 0.009 when infused on day 3). Anastomotic levels of transforming growth factor-β1 were also increased in the group receiving the transforming growth factor-β1 gene on day 3 (214 ± 66 vs. 135 ± 24, P = 0.02). CONCLUSIONS: Gene transfer into the healing colonic anastomosis can be effectively achieved via intraluminal administration of adenoviral vectors. Transfer of transforming growth factor-β1 increased the strength of colonic anastomoses when given at Day 3 but not at Day 0, demonstrating its diverse effects in the wound healing sequence. Thus, gene transfer of transforming growth factor-β1 may avoid the need for a diverting stoma in cases of rectal surgery and impaired healing resulting from chemotherapy or radiation.",
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Effect of adenoviral-mediated transfer of transforming growth factor-β1 on colonic anastomotic healing. / Migaly, John; Lieberman, Jonathan; Long, Walter; Fisher, Carol; Rolandelli, Rolando.

In: Diseases of the Colon and Rectum, Vol. 47, No. 10, 01.10.2004, p. 1699-1705.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of adenoviral-mediated transfer of transforming growth factor-β1 on colonic anastomotic healing

AU - Migaly, John

AU - Lieberman, Jonathan

AU - Long, Walter

AU - Fisher, Carol

AU - Rolandelli, Rolando

PY - 2004/10/1

Y1 - 2004/10/1

N2 - PURPOSE: Transforming growth factor-β1 plays a central role in colonic repair. We examined the temporal effect of vector-mediated transfer of transforming growth factor-β1 on colonic anastomotic healing. METHODS: Male Sprague-Dawley rats (n = 24) underwent transection of the distal colon and single-layer anastomosis. Proximal to the anastomosis, the colon was again transected and a colostomy was matured proximally. The distal colon was intubated with a silicone catheter, tunneled along subcutaneous tissues, and connected to a swivel apparatus for postoperative luminal infusion. Rats were randomized into four groups (n = 6 each). Two control groups received 10 10 plaque-forming units of a Type 5 E1-deleted adenovirus carrying the bacterial β-galactosidase gene either immediately following surgery or on postoperative Day 3. The treatment groups received transforming growth factor-β1 with the same viral construct at parallel time points. On postoperative Day 6, anastomotic bursting pressure and site were determined in situ with the anastomotic tissue subsequently harvested and analyzed by enzyme-linked immunosorbent assay for β-galactosidase and transforming growth factor-β1. RESULTS: When compared with its corresponding control, the group that received the transforming growth factor-β1 gene on postoperative day 3 had a significantly higher bursting pressure (mmHg; 119 ± 16 vs. 160 ± 12, mean ± SD; P = 0.001). While the majority of colons (5/6) from the control group burst at the anastomosis, none of the colons in the group that received transforming growth factor-β1 on day 3 burst at the anastomotic site (P = 0.007). β-Galactosidase levels (pg/ml) in anastomotic tissue were significantly increased in both control groups when compared with their respective treatment groups (101 ± 43 vs. 38 ± 30, P = 0.01 when infused the day of surgery and 243 ± 92 vs. 50 ± 30, P = 0.009 when infused on day 3). Anastomotic levels of transforming growth factor-β1 were also increased in the group receiving the transforming growth factor-β1 gene on day 3 (214 ± 66 vs. 135 ± 24, P = 0.02). CONCLUSIONS: Gene transfer into the healing colonic anastomosis can be effectively achieved via intraluminal administration of adenoviral vectors. Transfer of transforming growth factor-β1 increased the strength of colonic anastomoses when given at Day 3 but not at Day 0, demonstrating its diverse effects in the wound healing sequence. Thus, gene transfer of transforming growth factor-β1 may avoid the need for a diverting stoma in cases of rectal surgery and impaired healing resulting from chemotherapy or radiation.

AB - PURPOSE: Transforming growth factor-β1 plays a central role in colonic repair. We examined the temporal effect of vector-mediated transfer of transforming growth factor-β1 on colonic anastomotic healing. METHODS: Male Sprague-Dawley rats (n = 24) underwent transection of the distal colon and single-layer anastomosis. Proximal to the anastomosis, the colon was again transected and a colostomy was matured proximally. The distal colon was intubated with a silicone catheter, tunneled along subcutaneous tissues, and connected to a swivel apparatus for postoperative luminal infusion. Rats were randomized into four groups (n = 6 each). Two control groups received 10 10 plaque-forming units of a Type 5 E1-deleted adenovirus carrying the bacterial β-galactosidase gene either immediately following surgery or on postoperative Day 3. The treatment groups received transforming growth factor-β1 with the same viral construct at parallel time points. On postoperative Day 6, anastomotic bursting pressure and site were determined in situ with the anastomotic tissue subsequently harvested and analyzed by enzyme-linked immunosorbent assay for β-galactosidase and transforming growth factor-β1. RESULTS: When compared with its corresponding control, the group that received the transforming growth factor-β1 gene on postoperative day 3 had a significantly higher bursting pressure (mmHg; 119 ± 16 vs. 160 ± 12, mean ± SD; P = 0.001). While the majority of colons (5/6) from the control group burst at the anastomosis, none of the colons in the group that received transforming growth factor-β1 on day 3 burst at the anastomotic site (P = 0.007). β-Galactosidase levels (pg/ml) in anastomotic tissue were significantly increased in both control groups when compared with their respective treatment groups (101 ± 43 vs. 38 ± 30, P = 0.01 when infused the day of surgery and 243 ± 92 vs. 50 ± 30, P = 0.009 when infused on day 3). Anastomotic levels of transforming growth factor-β1 were also increased in the group receiving the transforming growth factor-β1 gene on day 3 (214 ± 66 vs. 135 ± 24, P = 0.02). CONCLUSIONS: Gene transfer into the healing colonic anastomosis can be effectively achieved via intraluminal administration of adenoviral vectors. Transfer of transforming growth factor-β1 increased the strength of colonic anastomoses when given at Day 3 but not at Day 0, demonstrating its diverse effects in the wound healing sequence. Thus, gene transfer of transforming growth factor-β1 may avoid the need for a diverting stoma in cases of rectal surgery and impaired healing resulting from chemotherapy or radiation.

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