Peripheral Blood Mononuclear Cells Therapy for Treatment of Lower Limb Ischemia in Diabetic Patients: A Single-Center Experience

Persiani, Francesca; Paolini, Alessandra; Camilli, Daniele; Mascellari, L.; Platone, A; Magenta, Alessandra; Furgiuele, Sergio

doi:10.1016/j.avsg.2018.05.036

Cited by 30 publications

(39 citation statements)

References 26 publications

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“…For treatment of patients with CLI, various clinical trials using progenitor cells isolated from bone marrow or peripheral blood have been made. 31,32 Although the cell therapy of CLI significantly improved clinical parameters in majority of the studies, the therapeutic efficacy of primary progenitor cells is highly variable from patient to patient due to its heterogeneity. Therefore, differentiation of iPSC to specific cell types is highly useful approach for treatment of ischemic diseases.…”

Section: Discussionmentioning

confidence: 99%

Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia

Park

Kwon

Kim

et al. 2020

Stem Cells Translational Medicine

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Critical limb ischemia is a condition in which tissue necrosis occurs due to arterial occlusion, resulting in limb amputation in severe cases. Both endothelial cells (ECs) and vascular smooth muscle cells (SMCs) are needed for the regeneration of peripheral arteries in ischemic tissues. However, it is difficult to isolate and cultivate primary EC and SMC from patients for therapeutic angiogenesis. Induced pluripotent stem cells (iPSCs) are regarded as useful stem cells due to their pluripotent differentiation potential. In this study, we explored the therapeutic efficacy of human iPSC‐derived EC and iPSC‐derived SMC in peripheral artery disease model. After the induction of mesodermal differentiation of iPSC, CD34+ progenitor cells were isolated by magnetic‐activated cell sorting. Cultivation of the CD34+ progenitor cells in endothelial culture medium induced the expression of endothelial markers and phenotypes. Moreover, the CD34+ cells could be differentiated into SMC by cultivation in SMC culture medium. In a murine hindlimb ischemia model, cotransplantation of EC with SMC improved blood perfusion and increased the limb salvage rate in ischemic limbs compared to transplantation of either EC or SMC alone. Moreover, cotransplantation of EC and SMC stimulated angiogenesis and led to the formation of capillaries and arteries/arterioles in vivo. Conditioned medium derived from SMC stimulated the migration, proliferation, and tubulation of EC in vitro, and these effects were recapitulated by exosomes isolated from the SMC‐conditioned medium. Together, these results suggest that iPSC‐derived SMC enhance the therapeutic efficacy of iPSC‐derived EC in peripheral artery disease via an exosome‐mediated paracrine mechanism.

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Section: Discussionmentioning

confidence: 99%

Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia

Park

Kwon

Kim

et al. 2020

Stem Cells Translational Medicine

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“…We also hope this study offers a reference for the non-surgical patients. Although revascularisation has been the most effective treatment for patients with CLI, some patients’ arteries are impossible to revascularise and require other treatments such as drugs, 26 transcutaneous electrical stimulation, 27 peripheral blood mononuclear cells therapy 28 or lumbar sympathectomy 29 to relieve pain and/or increase peripheral perfusion to avoid amputation. For those patients with non-reconstructable arteries, long-term PCRA may be less invasive and adequate for both analgesia and perfusion.…”

Section: Discussionmentioning

confidence: 99%

Perioperative patient-controlled regional analgesia versus patient-controlled intravenous analgesia for patients with critical limb ischaemia: a study protocol for a randomised controlled trial

Chen

Liu

et al. 2020

BMJ Open

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IntroductionBoth regional analgesia and intravenous analgesia are frequently used perioperatively for patients with critical limb ischaemia (CLI). Nevertheless, the comparison of perioperative effect of regional and intravenous analgesia has not yet been thoroughly illustrated. This study will comprehensively compare patient-controlled regional analgesia (PCRA) and patient-controlled intravenous analgesia (PCIA) as two different perioperative analgesia approaches for patients with CLI. It investigates their effects on analgesia, reperfusion and the quality of recovery perioperatively, also aims to provide clinical evidence to those non-surgical patients with non-reconstructable arteries.Methods and analysisThis trial is a randomised, single-centre, open-label, parallel trial with target sample size of 52 in total. Eligible participants will be randomly allocated to the PCRA group (group R) or the PCIA group (group I) after admission. Participants in group R will receive ultrasound-guided subgluteal sciatic catheterisation, followed by continuous PCRA infusion (0.2% ropivacaine 15 mL as loading dose, 8 mL/hour as background with a patient-controlled bolus of 6 mL). Participants in group I will receive PCIA (morphine is given in boluses of 1 mg as needed, background infusion at 1 mg/hour). Data will be collected at baseline (T0), 2 hours before revascularisation treatment (T1) and 2 hours before discharge (T2). The primary outcomes include the Numerical Rating Scale pain score at T1 and T2. The secondary outcomes include the perioperative transcutaneous oxygen pressure, the Tissue Haemoglobin Index, Hospital Anxiety and Depression Scale at T1 and T2; the Patient Global Impression of Change and patient satisfaction at T1 and T2; the perioperative cumulative morphine consumption, the length of postoperative hospital stay and adverse events.Ethics and disseminationThis study received authorisation from the Institutional Review Board of Peking Union Medical College Hospital on 21 March 2017 (approval no. ZS-1289X). Study findings will be disseminated through presentations at scientific conferences or publications in peer-reviewed journals.Trial registration numberChinese Clinical Trial Registry (ChiCTR2000029298).Protocol versionV.4CP.B2 (15 June 2020).

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“…PB-MNCs rappresent a new promising autologous therapy used in critical limb ischemia [14][15][16]48], diabetic foot [49][50][51] and chronic ulcers [52,53]. The angiogenic and arteriogenic potency of monocytes is well described [17,18,20,21,54].…”

Section: Discussionmentioning

confidence: 99%

“…This tecnique is less invasive in comparison to adipose tissue transplantation, faster, not operator-dependent and user-friendly. Promising results on the wound healing were obtained by this cellular concentrate in different clinical trials on critical limb ischemia patients, [14][15][16]. It has been observed that PB-MNCs are able to induce therapeutic angiogenesis to promote collateral vessel formation through paracrine effect [17,18].…”

Section: Introductionmentioning

confidence: 96%

The use of Peripheral Blood-Mononuclear Cells in Scleroderma patients: an observational preliminary study

Carella

Rossi

Ribuffo

et al. 2020

Preprint

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Background Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy and excessive production of collagen, which lead to skin and visceral fibrosis. The aim of our study is to assess the potential benefits of peripheral blood mononuclear cells (PB-MNCs) implants in the treatment of clinical manifestations such as mouth impairment, hand disability, digital ulcers and Raynaud’s phenomenon in Scleroderma patients. Methods From February 2016 to May 2019, 10 female patients were enrolled from the outpatient clinic of the Plastic Surgery Unit of Sapienza University of Rome. Parameters evaluated were: patients’ disability, using the Health Assessment Questionnaire (HAQ) disability index (DI) and the scleroderma HAQ (sHAQ); mouth opening capacity, by measuring the maximum interincisal distance and the mouth perimeter; hand mobility, assessed with clinical exam and the Hand Mobility in Scleroderma (HAMIS) scale; Raynaud’s phenomenon, evaluated through nailfold capillaroscopy; digital ulcers, examined through their features and incidence of appearance. SPSS software was used for a simple descriptive statistical analysis performed by the Student's paired t-test. P values less than 0.05 were considered statistically significant. Results The treatment showed a significant improvement of all the parameters evaluated at 1-year follow-up, it was well-tolerated by all the patients and the only complications noticed were small areas of ecchymosis. Conclusions Our results suggest that PB-MNCs injection could represent a treatment option to take into account for SSc patients. The procedure we used is easy and fast to perform, minimally invasive and not-operator dependent. We hope our observational and preliminary study could be considered as a starting point for further research studies.

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Peripheral Blood Mononuclear Cells Therapy for Treatment of Lower Limb Ischemia in Diabetic Patients: A Single-Center Experience

Cited by 30 publications

References 26 publications

Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia

Coadministration of endothelial and smooth muscle cells derived from human induced pluripotent stem cells as a therapy for critical limb ischemia

Perioperative patient-controlled regional analgesia versus patient-controlled intravenous analgesia for patients with critical limb ischaemia: a study protocol for a randomised controlled trial

The use of Peripheral Blood-Mononuclear Cells in Scleroderma patients: an observational preliminary study

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