Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer
Abstract
:1. Introduction
2. Diabetes Mellitus and Its Associated Diseases
2.1. Peripheral Polyneuropathy
2.2. Peripheral Vascular Disease
2.3. Macroangiopathy
2.4. Microangiopathy
3. Treatment Therapies for Diabetic Foot Ulcers
4. Stem Cell Therapy
4.1. Autologous Stem Cells
4.1.1. Bone Marrow-Derived Stem Cells
4.1.2. Peripheral Blood Stem Cells and Granulocyte Colony-Stimulating Factor
4.1.3. Adipose-Derived Mesenchymal Stem Cells
4.2. Allogeneic Stem Cells
4.2.1. Human Umbilical Cord Mesenchymal Stem Cells
4.2.2. Placental-Derived Mesenchymal Stem Cells
4.2.3. Embryonic Stem Cells
4.3. Routes of Administration
5. Cell Secretome: A Promising Therapeutic Alternative in Wound Healing
6. Bionanomaterials: A Modality for Stem Cell-Based Therapy Application
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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---|---|---|---|---|---|
Kirana et al. 2012 [21] | 24 patients with DFU 2 treatment groups: - Bone marrow mononuclear cells (BMCs) - Tissue repair cells | Autologous BMMSC | - Intramuscular injection - Intraarterial | - Both groups had improvement in wound healing without a significant difference. - Improvement in TcPO2 was detected in both groups. | 45 weeks |
Marino et al. 2013 [124] | 20 patients with PAD with chronic ulcers of the lower limb - 10 patients treated with AMSCs extracted by celution method | Autologous AMSCs | Local perilesional injection | - Six out of ten had complete healing. - Closure of the ulcer was observed. | 90 days |
Qin et al. 2016 [55] | 53 patients - 2 groups: control group, experimental group - Both groups received angioplasty; those in the experimental group also received HUCMSCs | Allogeneic HUCMSCs | - Intraarterial infusion - Intramuscular | Experimental group had significant improvement in: - Skin temperature - Ankle-brachial pressure index - Transcutaneous oxygen tension- Claudication distance | 1–3 months |
Xu and Liang 2016 [125] | 127 patients were treated with - Granulocyte colony-stimulating factor (G-CSF). - Extracted PBSC suspension | - G-CSF - Autologous PBSCs | Injection into the ischemic lower extremities at multiple points around the embolized blood vessels | Ischemic area of the patients was improved significantly. | 4 weeks |
Zeng et al. 2017 [120] | 57-year old patient with DFU - PDMSC hydrogel | Allogeneic PDMSCs | Topical | - Healing of foot ulcer was observed. - Walking foot function was well preserved. | 6 months |
Wu et al. 2018 [76] | A 54-year-old patient with DFU. Received standard treatment including debridement, dressing, and continuous negative pressure suction followed by autologous platelet-rich gel (APG) and BMMSC transplantation | Autologous BMMSCs | Local perilesional injection | Significant improvement of wound and complete healing was detected. | 30 days |
Zhao et al. 2020 [126] | 12 patients with DFU | - Allogeneic umbilical cord mesenchymal stem cells (UCMSCs) - Umbilical cord blood-derived endothelial colony-forming cells (ECFCs) | Local injection | - Accelerated healing in wounds treated with combination therapy was observed. - Wound size reduction was detected. | 1–4 weeks |
Scatena et al. 2021 [81] | 76 no-option critical ischemia (NO-CLI) patients DFUs - All patients treated with the same standard care (control group); - 38 patients were also treated with autologous PBMNC implants | Autologous PBMNC | - Intramuscular - Local peri -lesional injection | - Four out 38 amputations (10.5%) in the PBMNC group were done. - 15 out of 38 amputations (39.5%) in the control group (p = 0.0037) were done. - At 2 years follow-up, 80% of the PBMNC group was still alive vs. only 20% of the control group (p = 0.000). - 33 patients healed (86.6%) in the PBMNC group. - One patient healed in the control group. | 2 years |
Carstens et al. 2021 [67] | 63 patients with type 2 diabetes with chronic DFU—all amputation candidates - Treated with 30 × 106 SVF cells | Autologous adipose-derived stromal vascular fraction (SVF) | - Paravascular injection (pedal arteries) - Local perilesional injection | - At 6 months, 59 of the 63 subjects enrolled were evaluable for closure. - Fifty of the evaluable subjects achieved closure at 12 months (93%; confidence interval = 0.813–0.976). - The remaining four evaluable subjects had wound closure of ≥85%. | 6–12 months |
Chiang et al. 2021 [59] | Meta-analysis: - Authors assessed randomized controlled trials (RCTs), and extracted data on complete healing rate, amputation rate, and outcomes regarding peripheral circulation. - Extracted data pooled using a random-effects model - A total of 28 RCTs were eligible | Autologous stem cell therapy (ASCT) | Intramuscular | - ASCT significantly improved complete wound healing rate as compared with standard treatment for lower extremity chronic wounds (LECWs). - ASCT could promote the healing of LECWs. | 1–5 months |
Khalil et al. 2021 [106] | 10 patients with an open DFU wound 2 groups: - Group A: injected with PRF alone - Group B: injected with AMSC embedded in PRF | Autologous AMSCs | Topical | Group B had better healing index than group A. | 2–4 months |
Uzun et al. 2021 [127] | 20 patients with DFU 2 groups: AMSCs, standard wound care | Allogeneic adipose-derived mesenchymal stem cells | Local intra -lesional injection | Treatment group had better and faster wound healing compared to control. | 48 months |
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El Hage, R.; Knippschild, U.; Arnold, T.; Hinterseher, I. Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer. Biomedicines 2022, 10, 1507. https://doi.org/10.3390/biomedicines10071507
El Hage R, Knippschild U, Arnold T, Hinterseher I. Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer. Biomedicines. 2022; 10(7):1507. https://doi.org/10.3390/biomedicines10071507
Chicago/Turabian StyleEl Hage, Racha, Uwe Knippschild, Tobias Arnold, and Irene Hinterseher. 2022. "Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer" Biomedicines 10, no. 7: 1507. https://doi.org/10.3390/biomedicines10071507
APA StyleEl Hage, R., Knippschild, U., Arnold, T., & Hinterseher, I. (2022). Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer. Biomedicines, 10(7), 1507. https://doi.org/10.3390/biomedicines10071507