The use of cell and tissue grafts in the complex treatment of patients with pancreatic necrosis

Acute pancreatitis is a severe disease, which results in necrosis of part of the pancreas or the whole organ and causes a high mortality rate among patients

The severity of the disease, the reduction of general and local reparative processes and immune reactivity in patients with necrotic pancreatitis, the low effectiveness of conventional treatment methods, including surgery, became the background for developing a new method for treating pancreatic necrosis using allogeneic cryopreserved umbilical cord blood stem cells (UCBSCs) and allogeneic cryopreserved umbilical cord tissue (UCT)

UCBSCs secrete a large number of bioactive molecules which have possible anti-inflammatory, antifibrotic and wound-healing effects and can slow the progress of the disease

Study aim. The purpose of the clinical study was to increase the effectiveness of complex treatment of patients with pancreatic necrosis through systemic and local stimulation of reparative regeneration processes using intravenous administration of the cryopreserved allogeneic umbilical cord blood total nucleated cells (UCB-TNCs) and local transplantation of cryopreserved allogeneic UCT

Primary Endpoint:

  • Safety and effectiveness of cryopreserved allogeneic UCB-TNCs and UCT transplantation
  • Safety and effectiveness of cryopreserved allogeneic UCB-TNCs and UCT transplantation were evaluated by reviewing the clinical outcomes and adverse events in the postoperative period and every six months after inpatient treatment during a three year period
  • Major adverse events were adjudicated for observation: gastrointestinal bleeding, multiple organ failure, death

Dosing regimen: intravenous injection of 0,45·109 UCB-TNCs once a day for 5 days (CD34+cells – no less 1,0±0,01·103/ml) in 200 ml of normal saline solution (n = 73)

Cryopreserved allogeneic UTC was used as a surgical graft to close pancreatic fistulas and improve healing. The UTC transplantation was performed on the residual pancreatic tissue from all sides by surgical procedure. The graft was removed on 2-3 days after surgery

No HLA matching or immunosuppression required

Results:

1. The use of minimally invasive surgery under ultrasound guidance, followed by the infusion of UCB-TNCs, led to a 1.65 fold (р<0.05) increase in cured patients who were able to avoid open surgery. 2. The duration of their hospital stay was shortened 1.47-fold (р<0.05) compared with control group.3. The UCB-TNCs-treated patients who went to the second stage of open surgery were able to postpone needed surgery, which contributed to improved outcome. 4. The overall mortality of UCB-TNCs-treated patients was 2.06-fold (р<0.05) lower compared with control group, and their duration of post-operative hospital stay was 1.83-fold lower (р<0.05). 5. Among patients with necrotic pancreatitis, who received UCB-TNCs infusions and cord tissue grafts showed 4.71-fold (р<0.001) lower incidence of gastrointestinal bleeding from the abdominal cavity compared with control group. 6. During the five days of UCB-TNCs infusions, the early mortality of study patients from enzymatic toxemia was decreased 1.98-fold (р<0.05). 7. The development of disseminated intravascular coagulation syndrome in patients treated with UCB-TNCs occurred 3.48-fold (р<0.001) less often compared with control group. 8. The frequency of postoperative complications in the control group of patients associated with infection, impaired microcirculation, and the direct effect of pancreatic enzymes that fell in the abdominal cavity was 48.1 % versus 24.7 % in UCB-TNCs – treated group

Publication:

  • Kebkalo A.B. Surgery and cellular technologies in the complex treatment of patients with pancreatic necrosis. Klin Khir. 2012; (10):53-6. [Article in Russian]
  • Kebkalo A.B. Evaluation of clinical efficcacy of complex treatment for necrotic pancreatitis using cord blood stem cell transplantation and cryopreserved cord tissue. UkrJSurg. 2013; 2(21):47-53. [Article in Russian]
  • Kebkalo A.B., Lobintseva G.S., Seminog V.I., Shabliy V.A. The cord blood and umbilical cord use in the complex treatment of patients with pancreatic necrosis. UkrJEmergMed named after G. O. Mozhaev. 2012; 13(1):77-85. [Article in Russian]
  • Kebkalo A.B., Mamchych V.I., Lobyntseva G.S., Shabliy V.A. The effect of cord blood stem cells on the system of haemostasis in patients with different stages of necrotic pancreatitis. Ukr J Clin Lab Med. 2011, 6 (1): 67-73. [Article in Ukrainian]
  • Kebkalo A.B., Lobintseva G.S., Shabliy V.A. Cord blood and umbilicum in the complex treatment of patients with pancreatic necrosis. Ukr J Emergency Med named after G.O.Mozhaev, 2011, 12 (1):54-61. [Article in Ukrainian]
  • Kebkalo A.B. Evaluation of clinical efficcacy of complex treatment for necrotic pancreatitis using cord blood stem cell transplantation and cryopreserved cord tissue. Ukr J Surg. 2013, 21 (2): 47-53. [Article in Ukrainian]
  • Kebkalo A.B., Salyutin R.V., Lobintseva G.S. Biochemical changes in the blood plasma of patients with pancreatitis necrotizing transplantation of stem cells cord blood. Med Today and Tomorrow. 2011, 1–2: 50–51. [Article in Ukrainian]

The use of cell and tissue grafts in the complex treatment of patients with pancreatic necrosis

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