Cellular-Based Therapies in Systemic Sclerosis: From Hematopoietic Stem Cell Transplant to Innovative Approaches
Abstract
:1. Introduction
2. Hematopoietic Stem Cell Transplantation
3. Adoptive Cellular Therapies
4. Mesenchymal Stem Cells (MSC)
4.1. Intravenous MSCs Use
4.2. Loco-Regional MSCs Use
5. Regulatory T Cells and Chimeric Antigen Receptor T Cells
6. Tolerogenic Dendritic Cells
7. Open Questions and Future Perspectives
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Ethics Statement
Additional Information
References
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MSC Isolation | Administration Route | Source | Treated Patients | Clinical Target | Outcome | Major Adverse Events | References |
---|---|---|---|---|---|---|---|
BM-derived MSCs | Intravenous | Allo | 1 | Severe diffuse SSc | Ulcer healing and improved skin elasticity/vascularization | None | Christopeit et al., 2008 |
BM-derived MSCs | Intravenous | Allo | 5 | Severe diffuse SSc | All patients had temporary clinical improvement | Minor respiratory infection | Keyzer et al., 2011 |
BM-derived MSCs | Intravenous | Allo | 20 | Severe diffuse SSc | 15 patients showed sustained improvement in skin thickness | None | Farge et al., 2022 |
BM-derived MSCs and peripheral blood MSCs | Intramuscular injection | Auto | 6 (4 SSc, 2 mixed connective tissue disease) | Severe ischaemia and necrosis in fingers and/or toes | Pain relief in 5/6 patients | None | Kamata et al., 2007 |
BM-derived MSCs and peripheral blood MSCs | Intramuscular injection | Auto | 2 | Severe digital and malleolar ulcers | All had improvements with ulcers healing, pain relief, reduction of RP | None | Nevskaya et al., 2009 |
BM-derived MSCs and peripheral blood MSCs | Intramuscular injection | Auto | 46 (24 SSc, 22 other connective tissue diseases) | Severe digital ulcers | 20/23 SSc patients had improvement in pain and ulcers | None | Takahashi et al., 2009 |
BM-derived MSCs | Intramuscular injection | Auto | 8 | Severe digital ulcers | All had ulcers size and pain improvement | None | Ishigatsubo et al., 2010 |
BM-derived MSCs | Intramuscular injection | Auto | 40 (11 SSc, 29 with arteriosclerosis obliterans) | Severe digital ulcers | All had pain and trans-cutaneous oxygen tension improvement | Major limb amputation due to pre-existing osteomyelitis | Takagi et al., 2014 |
Adipose derived cell fractions | Subcutaneous injection | Auto | 13 | Raynaud’s phenomenon | 10 patients had clinical benefit, 3 reported no changes. | None | Bank et al., 2014 |
Adipose derived cell fractions | Subcutaneous injection | Auto | 20 | Peri-oral fibrosis | All patients had improved skin elasticity and vascularization | Small areas of ecchymosis | Del Papa et al., 2015 |
Adipose derived cell fractions | Subcutaneous injection | Auto | 15 | Severe digital ulcers | All patients displayed clinical benefit with fast healing of digital ulcers | None | Del Papa et al., 2015 |
Adipose derived cell fractions plus platelet-rich plasma | Subcutaneous injection | Auto | 6 | Peri-oral fibrosis | All patients had improved skin elasticity and vascularization | None | Virzì et al., 2017 |
Adipose derived cell fractions | Subcutaneaous/perioral injection | Auto | 6 | Skin scleroderma | Improvement in 4 patients, stabilization in all | None | Scuderi et al., 2013 |
Adipose derived cell fractions | Subcutaneous injection | Auto | 5 | Peri-oral fibrosis | All patients had improvement to perioral fibrosis | None | Onesti et al., 2016 |
Adipose derived cell fractions plus platelet-rich plasma | Subcutaneous injection | Auto | 7 | Peri-oral fibrosis | All patients had improvement to perioral fibrosis | None | Blezien et al., 2017 |
Adipose derived cell fractions | Subcutaneous injection | Auto | 62 | Peri-oral fibrosis | Improvement in mouth opening | Superficial wound infection | Almadori et al., 2019 |
SVF | Subcutaneous injection | Auto | 12 | Severe hand dysfunction | Improvement of pain, grasping capacity, finger oedema, Raynaud’s phenomenom, quality of life | None | Guillaume-Jugnot et al., 2016, Daumas et al., 2017, Granel et al., 2015 |
SVF | Subcutaneous injection | Auto | 18 | Severe hand dysfunction | Improvement of skin fibrosis, hand oedema, and quality of life | None | Park et al., 2020 |
Adipose derived cell fractions | Subcutaneous injection | Auto | 9 | Severe digital ulcers | All patients had pain improvement, digital ulcers improvement or healing | None | Del Bene et al., 2014 |
Adipose derived cell fractions vs placebo | Subcutaneous injection | Auto | 25 vs. 13 | Severe digital ulcers | 23/25 and 1/13 patients had digital ulcers improvement and healing, pain reduction and improvement on nail fold capillaroscopy | None | Del Papa et al., 2019 |
SVF vs placebo | Subcutaneous injection | Auto | 20 vs. 20 | Severe hand dysfunction | Improvement of hand function in both groups, with no superiority of the SVF | Hypoxaemia during the surgical process | Daumas et al., 2022 |
Adipose derived cell fractions vs placebo | Subcutaneous injection | Auto | 48 vs. 40 | Severe hand dysfunction | No improvement of hand function | Aspiration pneumonia, hypotension, angina | Khanna et al., 2022 |
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Xue, E.; Minniti, A.; Alexander, T.; Del Papa, N.; Greco, R.; on behalf of The Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT). Cellular-Based Therapies in Systemic Sclerosis: From Hematopoietic Stem Cell Transplant to Innovative Approaches. Cells 2022, 11, 3346. https://doi.org/10.3390/cells11213346
Xue E, Minniti A, Alexander T, Del Papa N, Greco R, on behalf of The Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT). Cellular-Based Therapies in Systemic Sclerosis: From Hematopoietic Stem Cell Transplant to Innovative Approaches. Cells. 2022; 11(21):3346. https://doi.org/10.3390/cells11213346
Chicago/Turabian StyleXue, Elisabetta, Antonina Minniti, Tobias Alexander, Nicoletta Del Papa, Raffaella Greco, and on behalf of The Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT). 2022. "Cellular-Based Therapies in Systemic Sclerosis: From Hematopoietic Stem Cell Transplant to Innovative Approaches" Cells 11, no. 21: 3346. https://doi.org/10.3390/cells11213346