A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells
Abstract Background Chronic limb-threatening ischemia (CLTI) represents the final stage of peripheral arterial disease. Approximately one-third of patients with CLTI are not eligible for conventional surgical treatments. Furthermore, patients with advanced stage of CLTI are prone to amputation and d...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-08-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-023-03427-z |
| _version_ | 1797577753896157184 |
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| author | Martha L. Arango-Rodríguez Ligia C. Mateus Claudia L. Sossa Silvia M. Becerra-Bayona Víctor Alfonso Solarte-David Miguel Enrique Ochoa Vera Lady T. Giratá Viviescas Ana M. Vera Berrio Sergio Eduardo Serrano Oliverio Vargas Andrés Catalá Isla Alape Benitez Germán Rangel |
| author_facet | Martha L. Arango-Rodríguez Ligia C. Mateus Claudia L. Sossa Silvia M. Becerra-Bayona Víctor Alfonso Solarte-David Miguel Enrique Ochoa Vera Lady T. Giratá Viviescas Ana M. Vera Berrio Sergio Eduardo Serrano Oliverio Vargas Andrés Catalá Isla Alape Benitez Germán Rangel |
| author_sort | Martha L. Arango-Rodríguez |
| collection | DOAJ |
| description | Abstract Background Chronic limb-threatening ischemia (CLTI) represents the final stage of peripheral arterial disease. Approximately one-third of patients with CLTI are not eligible for conventional surgical treatments. Furthermore, patients with advanced stage of CLTI are prone to amputation and death. Thus, an effective therapeutic strategy is urgently needed. In this context, autologous bone marrow mononuclear cell (auto-BM-MNC) and allogeneic mesenchymal stem cells represent a promising therapeutic approach for treating CLTI. In this study, we compared the safety and beneficial therapeutic effect of auto-BM-MNC versus allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) in diabetic patients with CLTI. Methods We performed a randomized, prospective, double-blind and controlled pilot study. Twenty-four diabetic patients in the advanced stage of CLTI (4 or 5 in Rutherford’s classification) and a transcutaneous oxygen pressure (TcPO2) below 30 mmHg were randomized to receive 15 injections of (i) auto-BM-MNC (7.197 × 106 ± 2.984 × 106 cells/mL) (n = 7), (ii) allo-WJ-MSCs (1.333 × 106 cells/mL) (n = 7) or (iii) placebo solution (1 mL) (n = 10), which were administered into the periadventitial layer of the arterial walls under eco-Doppler guidance. The follow-up visits were at months 1, 3, 6, and 12 to evaluate the following parameters: (i) Rutherford’s classification, (ii) TcPO2, (iii) percentage of wound closure, (iv) pain, (v) pain-free walking distance, (vi) revascularization and limb-survival proportion, and (vii) life quality (EQ-5D questionnaire). Results No adverse events were reported. Patients with CLTI who received auto-BM-MNC and allo-WJ-MSCs presented an improvement in Rutherford’s classification, a significant increase in TcPO2 values, a reduction in the lesion size in a shorter time, a decrease in the pain score and an increase in the pain-free walking distance, in comparison with the placebo group. In addition, the participants treated with auto-BM-MNC and allo-WJ-MSCs kept their limbs during the follow-up period, unlike the placebo group, which had a marked increase in amputation. Conclusions Our results showed that patients with CLTI treated with auto-BM-MNC and allo-WJ-MSCs conserved 100% of their limb during 12 months of the follow-up compared to the placebo group, where 60% of participants underwent limb amputation in different times. Furthermore, we observed a faster improvement in the allo-WJ-MSC group, unlike the auto-BM-MNC group. Trial registration This study was retrospectively registered at ClinicalTrials.gov (NCT05631444). |
| first_indexed | 2024-03-10T22:12:27Z |
| format | Article |
| id | doaj.art-7f8678c3c4704e9ab64196e44ee4b9fa |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-10T22:12:27Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-7f8678c3c4704e9ab64196e44ee4b9fa2023-11-19T12:33:48ZengBMCStem Cell Research & Therapy1757-65122023-08-0114111710.1186/s13287-023-03427-zA novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cellsMartha L. Arango-Rodríguez0Ligia C. Mateus1Claudia L. Sossa2Silvia M. Becerra-Bayona3Víctor Alfonso Solarte-David4Miguel Enrique Ochoa Vera5Lady T. Giratá Viviescas6Ana M. Vera Berrio7Sergio Eduardo Serrano8Oliverio Vargas9Andrés Catalá Isla10Alape Benitez11Germán Rangel12Banco Multitejidos y Centro de Terapias Avanzadas, Clínica FOSCAL InternacionalFundación Oftalmológica de Santander Carlos Ardila LulleFundación Oftalmológica de Santander Carlos Ardila LulleFacultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNABFacultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNABFacultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNABBanco Multitejidos y Centro de Terapias Avanzadas, Clínica FOSCAL InternacionalBanco Multitejidos y Centro de Terapias Avanzadas, Clínica FOSCAL InternacionalFacultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNABFundación Oftalmológica de Santander Carlos Ardila LulleFundación Oftalmológica de Santander Carlos Ardila LulleFundación Oftalmológica de Santander Carlos Ardila LulleFundación Oftalmológica de Santander Carlos Ardila LulleAbstract Background Chronic limb-threatening ischemia (CLTI) represents the final stage of peripheral arterial disease. Approximately one-third of patients with CLTI are not eligible for conventional surgical treatments. Furthermore, patients with advanced stage of CLTI are prone to amputation and death. Thus, an effective therapeutic strategy is urgently needed. In this context, autologous bone marrow mononuclear cell (auto-BM-MNC) and allogeneic mesenchymal stem cells represent a promising therapeutic approach for treating CLTI. In this study, we compared the safety and beneficial therapeutic effect of auto-BM-MNC versus allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) in diabetic patients with CLTI. Methods We performed a randomized, prospective, double-blind and controlled pilot study. Twenty-four diabetic patients in the advanced stage of CLTI (4 or 5 in Rutherford’s classification) and a transcutaneous oxygen pressure (TcPO2) below 30 mmHg were randomized to receive 15 injections of (i) auto-BM-MNC (7.197 × 106 ± 2.984 × 106 cells/mL) (n = 7), (ii) allo-WJ-MSCs (1.333 × 106 cells/mL) (n = 7) or (iii) placebo solution (1 mL) (n = 10), which were administered into the periadventitial layer of the arterial walls under eco-Doppler guidance. The follow-up visits were at months 1, 3, 6, and 12 to evaluate the following parameters: (i) Rutherford’s classification, (ii) TcPO2, (iii) percentage of wound closure, (iv) pain, (v) pain-free walking distance, (vi) revascularization and limb-survival proportion, and (vii) life quality (EQ-5D questionnaire). Results No adverse events were reported. Patients with CLTI who received auto-BM-MNC and allo-WJ-MSCs presented an improvement in Rutherford’s classification, a significant increase in TcPO2 values, a reduction in the lesion size in a shorter time, a decrease in the pain score and an increase in the pain-free walking distance, in comparison with the placebo group. In addition, the participants treated with auto-BM-MNC and allo-WJ-MSCs kept their limbs during the follow-up period, unlike the placebo group, which had a marked increase in amputation. Conclusions Our results showed that patients with CLTI treated with auto-BM-MNC and allo-WJ-MSCs conserved 100% of their limb during 12 months of the follow-up compared to the placebo group, where 60% of participants underwent limb amputation in different times. Furthermore, we observed a faster improvement in the allo-WJ-MSC group, unlike the auto-BM-MNC group. Trial registration This study was retrospectively registered at ClinicalTrials.gov (NCT05631444).https://doi.org/10.1186/s13287-023-03427-zPeripheral arterial diseaseChronic limb-threatening ischemiaCell therapyAutologous bone marrow mononuclear cells and allogenic Wharton jelly-derived mesenchymal stem cells |
| spellingShingle | Martha L. Arango-Rodríguez Ligia C. Mateus Claudia L. Sossa Silvia M. Becerra-Bayona Víctor Alfonso Solarte-David Miguel Enrique Ochoa Vera Lady T. Giratá Viviescas Ana M. Vera Berrio Sergio Eduardo Serrano Oliverio Vargas Andrés Catalá Isla Alape Benitez Germán Rangel A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells Stem Cell Research & Therapy Peripheral arterial disease Chronic limb-threatening ischemia Cell therapy Autologous bone marrow mononuclear cells and allogenic Wharton jelly-derived mesenchymal stem cells |
| title | A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells |
| title_full | A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells |
| title_fullStr | A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells |
| title_full_unstemmed | A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells |
| title_short | A novel therapeutic management for diabetes patients with chronic limb-threatening ischemia: comparison of autologous bone marrow mononuclear cells versus allogenic Wharton jelly-derived mesenchymal stem cells |
| title_sort | novel therapeutic management for diabetes patients with chronic limb threatening ischemia comparison of autologous bone marrow mononuclear cells versus allogenic wharton jelly derived mesenchymal stem cells |
| topic | Peripheral arterial disease Chronic limb-threatening ischemia Cell therapy Autologous bone marrow mononuclear cells and allogenic Wharton jelly-derived mesenchymal stem cells |
| url | https://doi.org/10.1186/s13287-023-03427-z |
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