Safety and Feasibility of Autologous and Allogeneic Cell Therapy in Preventing Wound Complications After Below-knee Amputation

Ischemic wound complications associated with below-knee amputation (BKA) necessitate conversion to above-knee (AKA) in up 36% of cases. Loss the knee joint has a deleterious impact on rehabilitation, independent living, and health care costs, thus ability promote productive healing BKA flap would be immense value. Cell therapy previously demonstrated pro-angiogenic benefits patients PAD, which may allow for improved healing. In order best assess value cell healing, this safety feasibility study was undertaken. A non-randomized, parallel-assignment, open-label conducted at single institution from January 2017 December 2020. Patients undergoing semi-elective due untreatable Rutherford 4 5 ischemia were recruited. Study participants placed one three arms: allogeneic bone marrow-derived mesenchymal stem (MSC) therapy, autologous concentrated marrow cells (BMC), control. Allogeneic MSCs obtained healthy female donors. Autologous BMCs via aspiration iliac crest, then closed centrifugation system. The product injected multiple intramuscular sites within gastrocnemius muscle 7 21 days prior BKA. Control did not receive placebo injection. followed 24 weeks postamputation. primary outcome treatment-related adverse events. Secondary outcomes included AKA use prosthetic limb. Thirty-four recruited study. Thirteen received MSC treatment, 6 BMC, 15 no treatment. Mean age 63.6 years, 88.2% males. Of patients, 94.1% had ischemia. Demographic disease-related characteristics are available Table I. Regarding outcomes, there Revision-free survival 79.4% weeks. This metric significantly reduced treatment group as compared control, but BMC or combined arm, seen II. Death, AKA, differ between groups. These results demonstrate an encouraging profile, events across all cohorts. There significant differences regards secondary revision walking status, though pilot powered detect these differences. Given potential benefit ambulation quality life, support larger phase II randomized trial.Table IDemographic control groupsControl (n = 15)Allogeneic 13)P valueAutologous 6)P valueAge, years62.8 ± 6.764.9 7.1.42663.0 5.8.947Male sex15 (100)9 (69.2).0206 (100)1.000Ethnicity African American5 (33.3)6 (46.2).4881 (16.7).445 White (non-Hispanic)10 (66.7)7 (53.8).4885 (83.3).445 (Hispanic)0 (0%)0 (0)>.9990 (0)>.999Rutherford category 40 (0)1 (7.7).2741 (16.7).105 515 (100)12 (92.3).2745 (83.3).105Smoking status Current5 (33.3)3 (23.1).5494 (66.7).163 Former7 (46.7)7 (53.8).7052 (33.3).577 Never3 (20)3 (23.1).8430 (0).237Past medical history Diabetes mellitus14 (93.3)8 (61.5).0416 (100).516 Myocardial infarction2 (13.3)2 (15.4).8770 (0).347 TIA stroke1 (6.7)2 (15.4).4571 (16.7).481 Coronary artery disease4 (26.7)3 (23.1).8270 (0).160 Congestive heart failure5 (23.1).5490 (0).105 DVT index leg2 Chronic kidney disease8 (53.3)9 (69.2).3902 (33.3).407 Hypertension15 (100)11 (84.6).1155 (83.3).105 Systolic blood pressure, mm Hg136.7 16.8114.4 20.5.005103.7 13.9<.001 Diastolic Hg76.1 12.466.4 16.7.09854.8 11.9.004Cardioprotective medication Statin11 (73.3)13 (100).0445 (83.3).627 Antiplatelet9 (60)12 (92.3).0495 (83.3).306 Anticoagulation8 (53.3)7 (53.8).9781 (16.7).125 Beta blocker8 Calcium channel blocker4 (26.7)2 (15.4).4684 (66.7).088 ACE inhibitor1 (6.7)3 (23.1).2164 (66.7).004ACE, Angiotensin-converting enzyme; cells; DVT, deep vein thrombosis; MSC, cell; TIA, transient ischemic attack.Data presented number (%) mean standard deviation.Boldface P values represent statistical significance.P comparison controls. means calculated using two-tailed t-tests, whereas proportions z-tests. Open table new tab IIPrimary groups weeksControl valueCombined 19)P valueTreatment-related events0 (0)0 (0)>.999Revision-free survival14 (93.3)7 (53.8).0166 (100).51713 (68.4).074Conversion AKA1 (6.7)4 (30.8).0970 (0).5174 (21.1).240Death0 (0)2 (15.4).1150 (0)>.9992 (10.5).195Walking prosthetic6 (40)3 (23.1).3391 (16.7).3064 (21.1).229AKA, Above knee; cell.Data (%).Boldface significance.The represents summed total increase sample power.P z-tests,