Bone marrow-derived mesenchymal stromal cells improve vascular regeneration and reduce leukocyte-endothelium activation in critical ischemic murine skin in a dose-dependent manner

Schweizer, Riccardo; Kamat, Pranitha; Schweizer, Dennis; Dennler, Cyrill; Zhang, Shengye; Schnider, Jonas; Salemi, Souzan; Giovanoli, Pietro; Eberli, Daniel; Enzmann, Volker; Erni, Dominique; Plock, Jan A.

doi:10.1016/j.jcyt.2014.05.008

Cited by 25 publications

(14 citation statements)

References 79 publications

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“…30 Recent research suggests that BMSC constitutively release several immunomodulatory factors that influence leukocyte function and modulate the activation state of endothelial cells. 31,32 We and others have shown that BMSC therapy accelerates wound closure and enhances survival of skin flaps after I/R injury. 23,33,34 However, the lack of real-time assessment of flap vascular perfusion change remains a major weakness in monitoring the efficacy of BMSC therapeutic I/R injury over time.…”

Section: Discussionmentioning

confidence: 95%

“…Such I/R injury may cause partial flap loss in Σ7% to 20% of free flaps and ∼20% to 33% of pedicled flaps . Recent research suggests that BMSC constitutively release several immunomodulatory factors that influence leukocyte function and modulate the activation state of endothelial cells . We and others have shown that BMSC therapy accelerates wound closure and enhances survival of skin flaps after I/R injury .…”

Section: Discussionmentioning

confidence: 97%

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Stem cells enhance reperfusion following ischemia: Validation using laser speckle imaging in predicting tissue repair

Tang¹,

Thompson²,

Nathan³

et al. 2018

The Laryngoscope

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 97%

Stem cells enhance reperfusion following ischemia: Validation using laser speckle imaging in predicting tissue repair

Tang¹,

Thompson²,

Nathan³

et al. 2018

The Laryngoscope

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“…Anesthesia and antidote reversion were achieved using triplemix injections as described previously. 9,10 Microdialysis microprobes (CMA20, 100 kDa; Polyethersylfone; CMA Microdialysis, Stockholm, Sweden) were inserted into the peritumoral tissue and perfused with Ringer/hydroxyethyl starch 6% (Fresenius, Oberdorf, Switzerland) using a microinjection pump (CMA/100; Polyethersylfone). The perfusion rate was set to 1 µl/minute as described previously.…”

Section: Microdialysismentioning

confidence: 99%

“…These cells have multiple functions, including the secretion of soluble factors through which they participate and contribute to immunomodulation, antiapoptosis, angiogenesis, and regeneration. [8][9][10] Because of these functionalities, local and migrating stem cells have been suspected to endorse breast cancer development. 11,12 Suggested by reports, adipose-derived mesenchymal stromal cells, and more in general mesenchymal stem cells, can promote progression and metastasis of breast cancer [13][14][15][16][17] through homing of stem cells to tumors as an evident process.…”

mentioning

confidence: 99%

Human Adipose-Derived Mesenchymal Stromal Cells May Promote Breast Cancer Progression and Metastatic Spread

Kamat

Schweizer

Kaenel

et al. 2015

Plastic and Reconstructive Surgery

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BACKGROUND: Stem cell-enriched fat grafting has been proposed as a potential therapy for reconstructive, restorative, or enhancement-related procedures of the breast. Its role in postoncologic breast reconstruction is still emerging, with concerns about safety. The authors investigated the dose-dependent interaction between human adipose-derived mesenchymal stromal cells (AD-MSCs) and human breast cancer cell (BCC) lines [MDA-MB-231 (MDA) and MCF-7 (MCF)] focusing on tumor microenvironment, tumor growth, and metastatic spread. METHODS: Adipose-derived mesenchymal stromal cell influence on viability and factor expression [regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-, and eotaxin) of breast cancer cells was studied in vitro using direct and indirect co-culture systems. Groups were formed according to adipose-derived mesenchymal stromal cell-to-cancer cell number ratio [MDA/MCF only, AD-MSC/(MDA/MCF), and AD-MSC/(MDA/MCF)]. A humanized orthotopic murine cancer model was used to evaluate breast cancer progression and metastasis (n = 10/group). Cells were injected into the mammary pad in different ratios and animals were monitored over 42 days. Microdialysis was performed to analyze RANTES levels in the tumor microenvironment (days 21 and 42). Primary and metastatic tumors were weighed and analyzed for oncogene, growth factor, and metastatic marker expression. RESULTS: MDA cell viability increased from 45.5 percent to 95.5 percent in presence of adipose-derived mesenchymal stromal cells in vitro. In vivo, animals with AD-MSC showed increased mean tumor weight (MDA, p < 0.01; MCF versus controls, p < 0.05) and metastatic occurrence (40 percent in MDA; 30 percent in MCF versus 0 percent in controls). Cytokine analysis revealed switching of MCF tumor phenotype to a more malignant type in the presence of adipose-derived mesenchymal stromal cells. CONCLUSION: Human adipose-derived mesenchymal stromal cells may promote progression and metastatic spread in breast cancer through a switch to a more malignant phenotype with worse prognosis. Methods: Adipose-derived mesenchymal stromal cell influence on viability and factor expression [regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-α, and eotaxin) of breast cancer cells was studied in vitro using direct and indirect co-culture systems. Groups were formed according to adipose-derived mesenchymal stromal cell-to-cancer cell number ratio [MDA/MCF only, AD-MSC

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“…The ability of MSCs in mitigating reperfusion injury has been attributed to paracrine anti-inflammatory effects [53], with reduction in I/R injury in skin flaps [54,55] and in renal I/R injury [56,57]. In the latter study, MSCs but not conditioned medium were able to ameliorate I/R injured kidneys, which is in line with own findings where BM-MSCs but not conditioned medium were anti-inflammatory on activated endothelium in a critically ischaemic skin flap [53]. Effective mitigation of I/R injury after cold ischaemia could promote VCA allocation over larger geographical distances, decreasing ischaemia-related time constraints and expanding VCA donor-pool.…”

Section: Routes Of Administrationmentioning

confidence: 99%

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

Schweizer

Gorantla

Plock

2015

Current Opinion in Organ Transplantation

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PURPOSE OF REVIEW Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. RECENT FINDINGS Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SUMMARY Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA. Purpose of review Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. Recent findingsExperimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSCinduced long-term operational tolerance in experimental VCA is mediated by induction of mixed donorspecific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SummaryCellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA.

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Bone marrow-derived mesenchymal stromal cells improve vascular regeneration and reduce leukocyte-endothelium activation in critical ischemic murine skin in a dose-dependent manner

Cited by 25 publications

References 79 publications

Stem cells enhance reperfusion following ischemia: Validation using laser speckle imaging in predicting tissue repair

Stem cells enhance reperfusion following ischemia: Validation using laser speckle imaging in predicting tissue repair

Human Adipose-Derived Mesenchymal Stromal Cells May Promote Breast Cancer Progression and Metastatic Spread

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

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