J. Chris Eagon

In Vivo Distribution of Human Adipose-Derived Mesenchymal Stem Cells in Novel Xenotransplantation Models

The potential for human adipose‐derived mesenchymal stem cells (AMSC) to traffic into various tissue compartments was examined using three murine xenotransplantation models: nonobese diabetic/severe combined immunodeficient (NOD/SCID), nude/NOD/SCID, and NOD/SCID/MPSVII mice. Enhanced green fluorescent protein was introduced into purified AMSC via retroviral vectors to assist in identification of cells after transplantation. Transduced cells were administered to sublethally irradiated immune‐deficient mice through i.v., intraperitoneal, or subcutaneous injection. Up to 75 days after transplantation, tissues were harvested and DNA polymerase chain reaction (PCR) was performed for specific vector sequences as well as for human Alu repeat sequences. Duplex quantitative PCR using human β‐globin and murine rapsyn primers assessed the contribution of human cells to each tissue. The use of the novel NOD/SCID/MPSVII mouse as a recipient allowed rapid identification of human cells in the murine tissues, using an enzyme reaction that was independent of surface protein expression or transduction with an exogenous transgene. For up to 75 days after transplantation, donor‐derived cells were observed in multiple tissues, consistently across the various administration routes and independent of transduction parameters. Tissue localization studies showed that the primary MSC did not proliferate extensively at the sites of lodgement. We conclude that human AMSC represent a population of stem cells with a ubiquitous pattern of tissue distribution after administration. AMSC are easily obtained and highly amenable to current transduction protocols for retroviral transduction, making them an excellent avenue for cell‐based therapies that involve a wide range of end tissue targets.

Absorbable Mesh Reinforcement of a Stapled Pancreatic Transection Line Reduces the Leak Rate with Distal Pancreatectomy

Pancreatic leak remains a significant cause of morbidity after distal pancreatectomy. We report the use of an absorbable mesh to reinforce a stapled pancreatic transection line for distal pancreatectomy. Forty consecutive distal pancreatectomies (33 open and 7 laparoscopic) were performed since the introduction of mesh reinforcement. We utilized an inclusive definition of pancreatic leak to critically evaluate the staple line reinforcement material. In addition, we compared the pancreatic leak rate for this case series with the antecedent 40 cases where mesh reinforcement was not available. In the prospective series there was 1 leak in 29 cases (3.5%) in which mesh reinforcement was utilized, and 4 leaks in 11 cases (36%) when mesh was not utilized (p < 0.005). The 12.5% leak rate for the 40 cases during the prospective period, compared favorably to the 27.5% leak rate for the 40 cases preceding the study period (p = 0.09). Twenty-nine cases receiving mesh compared favorably to the 23 stapled cases in the control series, reducing leak rate from 22 to 3.5% (p = 0.04). Mesh reinforcement of the stapled pancreatic transection line reduced the pancreatic leak rate after distal pancreatectomy. Mesh reinforcement was possible with open or laparoscopic resections. No complications were attributable to the use of absorbable mesh.

Hypercapnia improves tissue oxygenation in morbidly obese surgical patients

Risk of wound infection is increased in morbidly obese surgical patients, in part because a major determinant of wound infection risk, tissue oxygenation, is marginal. Unlike in lean patients, supplemental inspired oxygen (Fio2) only slightly improves tissue oxygenation in obese patients. Mild hypercapnia improves tissue oxygenation in lean patients but has not been evaluated in obese patients. We thus tested the hypothesis that mild hypercapnia markedly improves tissue oxygenation in morbidly obese patients given Fio2 80% during major abdominal surgery. Thirty obese patients (body mass index 61.5 ± 17 kg/m2) scheduled for open gastric bypass were randomly assigned to normocapnia (n = 15, end-tidal Pco2 35 mm Hg) or hypercapnia (n = 15, end-tidal Pco2 50 mm Hg); Fio2 was 80%. Anesthetic management and other confounding factors were controlled. Tissue oxygen tension was measured subcutaneously at the upper arm using a polarographic probe in a silastic tonometer. Demographic characteristics, cardiovascular measurements, and Pao2 (222 ± 48 versus 230 ± 68 mm Hg in normocapnic versus hypercapnic; mean ± sd; P = 0.705) were comparable in the groups. Tissue oxygen tension, however, was greater in hypercapnic than in normocapnic patients (78 ± 31 versus 56 ± 13 mm Hg; P = 0.029). Mild hypercapnia increased tissue oxygenation by an amount believed to be clinically important and could potentially reduce the risk of surgical wound infection in morbidly obese patients.