Adipose-derived stem cells in diabetic foot care: Bridging clinical trials and practical application

Table 1 Outcome of clinical trials on adipose-derived stem cells treatment for diabetic foot

Ref.	Country	Cell type	Condition	Intervention	Cell count	Follow-up	Enrollment	Outcome
Mrozikiewicz-Rakowska et al[55], 2023	Poland	Allogeneic	Ulcer	Hydrogel	2.5 × 106 cells	49 d	47	The time required for a 50% reduction in wound size was 17.6 ± 1.5 d (P = 0.029)
Lee et al[41], 2012	Korea	Allogeneic	Ischemia	Intramuscular injection	5 × 106 cells	6 months	15	66.7% of patients showed clinical improvement, with enhanced pain relief, increased claudication walking distance, and the development of vascular collateral networks
Moon et al[33], 2019	Korea	Allogeneic	Ulcer	Hydrogel	1 × 106 cells per film	12 wk	59	Wound closure reached 73% by week 8 and increased to 82% by week 12, with a median closure time of 28.5 d
Yastı et al[80], 2023	Türkiye	Autologous	Ulcer	3D-AMHAT	15-25 mL of fat	12 wk	20	All wounds, except one, were fully epithelialized by the ninth week, with a mean time to complete closure of 32.20 d
Bajuri et al[81], 2023	Malaysia	Autologous	Ulcer	3D-AMHAT	20 mL of fat	12 wk	10	Within 12 wk, complete healing was observed in 70% of the patients
Bura et al[31], 2014	France	Autologous	Ischemia	Intramuscular injection	1 × 108 cells	6 months	7	All ulcers showed 100% improvement after 6 months, with three completely healed
Uzun et al[82], 2021	Türkiye	Allogeneic	Ulcer	Injection	6 × 106 cells	4 years	20	90% healing, with no adverse reactions
Nolan et al[83], 2022	United Kingdom	Autologous	Ulcer	Intramuscular injection	/	4 wk	18	Increased mean microvessel density by + 32% to + 45% at 1 wk (P = 0.035)
Dreifuss et al[84], 2017	United States	Autologous	Pedal atrophy	Injection	/	12 months	23	Dermal thickness increased significantly post-injection, persisting through 24 months (P < 0.05)
Kress et al[85], 2023	United States	Autologous	Ulcer	Injection	13.9 mL of fat	9.3 months	10	Achieved full clinical recovery with no reulceration
Carstens et al[53], 2021	United States	Autologous	Ulcer	Subcutaneous injection	3 × 107 cells	12 months	63	At 6 months, 51 subjects achieved complete closure, and 8 had closure of ≥ 75%
Nilforoushzadeh et al[86], 2020	Iran	Autologous	Ulcer	Engineered skin graft	/	21 wk	5	There was a significant increase (P ≤ 0.05) in both skin thickness and vascular bed density
Lonardi et al[87], 2019	Italy	Autologous	Minor amputations	Injection	10-30 mL of fat	6 months	114	At 6 months, 80% of the feet showed healing (P = 0.0064)
Carstens et al[42], 2017	United States	Autologous	Ischemia	Intramuscular injection	/	12 months	10	All patients showed clinical improvement (rest pain, claudication, ABI)
Zollino et al[88], 2019	Italy	Autologous	Ulcer	Injection	15 mL of fat	24 wk	16	The average wound healing time was 17.5 ± 7.0 wk (P < 0.036)
Raposio et al[43], 2018	Italy	Autologous	Ischemia	Subcutaneous injection	5 × 105 cells	6 months	7	After 6 months, all patients demonstrated complete wound healing
Namgoong et al[89], 2010	Korea	Autologous	Ulcer	Hydrogel	30-50 mL of fat	16 wk	20	Eight out of 10 patients (80%) achieved complete wound healing after 16 wk, with a reduction in wound area by 4.3 ± 1.0 cm² (P = 0.043)
Han et al[90], 2010	Korea	Autologous	Ulcer	Subcutaneous injection	4.0-8.0 × 106 cells	8 wk	54	100% healing was achieved
Smith et al[91], 2020	United Kingdom	Autologous	Ulcer	Injection	2 mL of fat/cm²	21 months	18	There was no difference between any of the groups in terms of clinical outcomes
Gennai et al[92], 2021	Italy	Autologous	Minor amputations	Injection	10-30 mL of fat	6 months	114	The average hospital length of stay was 16.2 d (P = 0.025)

ABI: Ankle/brachial index.

Table 2 Comparison of adipose-derived stem cells administration methods for diabetic foot treatment

Method	Advantages	Disadvantages
Intravenous infusion	Targets multiple areas	Cells may get trapped in the lungs
Arterial injection	Direct delivery to the foot	Technically challenging and risk of blood vessel issues
Muscular injection	Directly reaches wound, good for poor blood flow, improves cell survival and nerve regeneration	Less effective for wounds away from muscle
Local injection	High cell concentration at the wound	Risk of uneven cell spread and clumping