Table 1 Published Clinical Trials
From: Adipose-derived stem cells for treatment of chronic ulcers: current status
Author, year, and country | Title | Cause of ulcers | Patients | Randomization and blinding | Type of ADSC | Application method | Primary endpoint | Follow-up | Conclusion |
|---|---|---|---|---|---|---|---|---|---|
Han et al. [28], 2010, Korea | The treatment of diabetic foot ulcers with uncultured, processed lipoaspirate cells: a pilot study | Peripheral artery disease (diabetes 100%) | 28 cases 26 controls Total 54 | Yes, open label | Adipose-derived stem cell (ADSC) pellet isolated using collagenase and centrifugation. Donor site: abdomen 4.0 × 106 to 8.0 × 106 cells | Same-day procedure. Dispersed onto the wound and sealed with fibrinogen, thrombin, and Tegaderm | Wound closure rate | 2 months | 100% of wounds healed in 8 weeks in the case group, 62% in the control group. No adverse events |
Lee et al. [29], 2012, Korea | Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: a pilot study | Peripheral artery disease. Thromboangiitis obliterans (80%) and diabetes (20%). 80% with chronic wounds | 15 cases 0 controls Total 15 | No, open label | Digested using collagenase and centrifugation. Cultured. Donor site: abdomen 3.0 × 108 cells. | 60 intramuscular injections under spinal anesthesia. Time from harvest to injection not mentioned in study | Absence of adverse events. Formation of collateral networks. Secondary endpoint: pain, amputation, healing of wounds | 6 months | Chronic wounds healed in 66.7% of patients. At 6 months, improvement in pain rating and in claudication walking distance. Five patients required minor amputation during follow-up, and all amputation sites healed completely. No adverse events |
Marino et al. [30], 2013 Italy | Therapy with autologous adipose-derived regenerative cells for the care of chronic ulcer of lower limbs in patients with peripheral arterial disease | Peripheral artery disease | 10 cases 10 controls Total 20 | No, open label | Freshly isolated using Celution® 800/CRS. Donor site: abdomen/inner thigh. 260 g lipoaspirate 1.5 × 106 cells | Same-day procedure. 5 mL injected in 1 cm deep injections around the ulcer under peripheral block of the sciatic nerve using a 10-mL syringe and 21-gauge needle | Complete healing of the ulcer | 3 months | Reduction in size, depth, and pain of all cases compared with controls. 6 of 10 cases had total healing, none in control group. No adverse events |
Bura et al. [31], 2014 France | Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia | Peripheral artery disease | 7 cases 0 controls Total 7 | No, open label | Isolated using collagenase, centrifugation and then cultured. Donor site: abdomen. (30Â g) 60Â mL lipoaspirate 108 cells | 14Â days after liposuction. 26Â mL injected in 30 intramuscular injections (15 in each muscle) into the internal and external gastrocnemius and anterior compartment of the ischemic leg using a 23-gauge needle | Improvement of wound healing | 6Â months | Ulcer size, ulcer number, and pain reduced. Improved transcutaneous saturation. No adverse events |
Raposio et al. [32], 2016 Italy | Adipose-derived stem cells added to platelet-rich plasma for chronic skin ulcer therapy | Venous (45%), ischemic (42%), diabetic (10%) and post-traumatic (3%) | 16 cases 24 controls Total 40 | Yes, open label | e-PRP from 42 cm3 of peripheral blood combined with ADSC from 80 mL of abdominal fat vibrated at 600 vibrations/min for 6 min and centrifuged at 52 g for 6 min. 5 × 105 cells | Same-day procedure. 5 mL injected in multiple injections around and under the ulcer using a 10-mL syringe | Wound closure rate | 18 months | Similar healing rates. Wound closure rates higher in case group. No adverse events |
Carstens et al. [33], 2017, Nicaragua | Non-reconstructable peripheral vascular disease of the lower extremity in ten patients treated with adipose-derived stromal vascular fraction cells | Peripheral artery disease (3 diabetes, 4 atherosclerosis, and 3 both) | 10 cases 0 controls Total 10 | No, open label | Fresh, non-fractioned, non-cultured. Enzymatic congestion using collagenase and centrifugation. Donor site: abdomen 250–350 cm3 fat. 19.1 to 157.8 × 106 cells | 3–4 mL administered using a 26-gauge needle into the plane between the gastrocnemius and soleus muscles in a pattern of injections (22 per muscle, 11 in the external and 11 in the internal gastrocnemius, each one 1.5 cm to 2 cm apart) of equal volume each (0.5 ml), on either side of the midline | Wound closure rate, pain | 18 months | 4 of 6 wounds closed within 9 months, one patient had a healing wound when she died at 4 months and 1 patient had a skin graft to close the wound at 5 months. Reduced pain in all patients. No adverse events |
Chopinaud et al. [34], 2017 France | Autologous adipose tissue graft to treat hypertensive leg ulcer: a pilot study | Hypertensive | 10 cases 0 controls Total 10 | No, open label | LipoStructure®. Freshly purified fat using centrifugation at 3000 rpm for 3 min. | Same-day procedure. Multiple injections around and under the ulcer with 0.8-mm cannula | Wound closure rate | 6 months | 73.2% median closure rate at 3 months, 93.1% at 6 months. Reduced fibrin, necrosis and pain. Increased granulation. No adverse events |
Konstantinow et al. [35], 2017 Germany | Therapy of ulcus cruris of venous and mixed venous arterial origin with autologous, adult, native progenitor cells from subcutaneous adipose tissue: a prospective clinical pilot study | Arterial-venous (9 patients), venous (7 patients). 6 patients with diabetes | 16 cases 0 controls Total 16 | No, open label | The Transpose RT™ Processing Unit (TPU) (InGeneron Inc., Houston, TX, USA) 30 mL lipoaspirate. Donor site: abdomen. 9–15 × 106 cells | Same-day procedure. 4 ml injected 5 to 10 mm deep into the central and bordering ulcer area using a 1-mL Luer-Lock syringe and a 24-gauge needle. Additionally, 2.5 mL applied on a collagen sponge onto the wound | Wound closure rate, pain | 6 months | All venous patients and four of nine arterial-venous patients had 100% wound closure within 9–26 weeks. Reduced wound pain in all patients within days of treatment. No adverse events |
Darinskas et al. [36], 2017 Lithuania | Stromal vascular fraction cells for the treatment of critical limb ischemia: a pilot study | Peripheral artery disease (7 patients with ulcers) (9 patients with diabetes) | 15 cases 0 controls Total 15 | No, open label | Uncultured ADSC isolated without collagenase using mechanical isolation (the fat minced using a metal mill and subsequent centrifugation) 40Â mL lipoaspirate Donor site: abdomen | One or two 20-mL syringes with minimum of 20 million viable cells per syringe and a minimum of 30 injections per syringe. Intramuscular injections along the arteries. Secondary injections were performed 2Â months after first application of cells | Wound closure rate, pain | 12Â months | All ulcers healed. Two patients had amputations. Reduced pain in all patients. 86.7% with improvement in walking distance. No adverse events |