Impact of Mesenchymal Stromal Cell Delivery Through Cardiopulmonary Bypass on Postnatal Neurogenesis

Maeda, Takuya; Sarkışlalı, Kamil; Leonetti, Camille; Kapani, Nisha; Dhari, Zaenab; Haj, Ibtisam Al; Ulrey, Robert; Hanley, Patrick J.; Jonas, Richard A.; Ishibashi, Nobuyuki

doi:10.1016/j.athoracsur.2019.08.036

Cited by 13 publications

(11 citation statements)

References 39 publications

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“…Allogeneic BM-MSCs may have cellular and humoral alloreactivity. 6 The present study; however, demonstrated that allogenic BM-MSC infusion did not change the subpopulation of lymphocytes immediately following CPB and 12 hours after CPB. BM-MSCs show low expression of major histocompatibility class II antigen.…”

Section: Discussioncontrasting

confidence: 68%

“…Then cells were expanded up to 6 total passages with the Quantum Cell Expansion system, which we described previously. 6 , 11 Before infusion, BM-MSCs were tested according to the minimal criteria to define human BM-MSC published by the International Society of Cellular Therapy. 12 …”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

“…5 Indeed, we have previously demonstrated that BM-MSC delivery through cardiopulmonary bypass (CPB) in a piglet model has the potential to mitigate the deleterious effect of CPB on neural stem/progenitor cells and to promote migration of neuroblasts toward the frontal cortex. 6 CPB results in a systemic inflammatory response syndrome due to blood exposure to nonendothelial surfaces. 7 In addition, our previous study using a neonatal piglet model has shown that CPB causes prolonged brainspecific inflammation.…”

mentioning

confidence: 99%

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Influence of administration of mesenchymal stromal cell on pediatric oxygenator performance and inflammatory response

Maeda¹,

Briggs

Datar³

et al. 2021

JTCVS Open

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Objective: Mesenchymal stromal cells have important immunomodulatory and neuroprotective properties. The aim of this study was to evaluate the feasibility of mesenchymal stromal cell administration into a cardiopulmonary bypass (CPB) circuit, including a pediatric oxygenator, and to assess the immunomodulatory response of the circulating blood prime. Methods: A bypass circuit with a pediatric oxygenator, including integral filter was primed with bank whole blood. Normal saline (control) or 120 × 10 6 mesenchymal stromal cells were injected into the venous reservoir after 80 minutes of perfusion. To assess oxygenator function, immune reaction, and cytokine/chemokine levels, the ex vivo circulation was maintained for 300 minutes after administration. Results: There were no differences in flow rate, trans-oxygenator pressure gradient, blood oxygen, and carbon dioxide levels between control and cell delivery groups. No adhesion of mesenchymal stromal cells was observed on the filter mesh by scanning electron microscopy. Lymphocyte surface marker assay found no difference in the number of B cells, T cells, or natural killer cells between the 2 groups, indicating no immunogenicity of allogeneic mesenchymal stromal cells under ex vivo CPB conditions. CPB significantly changed the level of interleukin (IL) 4, IL-6, IL-8, IP-10, macrophage colony stimulating factor, macrophage inflammatory protein-1 β , monocyte chemoattractant protein-1, and IL-1 α over time. IL-6 level was significantly increased after cell administration. Conclusions: The administration of mesenchymal stromal cells does not interfere with oxygenator function. Allogeneic mesenchymal stromal cells show no immunogenicity, and increase plasma IL-6 level during ex vivo circulation. Further investigation is necessary to determine the effect of mesenchymal stromal cell delivery through CPB during pediatric cardiac surgery.

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Section: Discussioncontrasting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Influence of administration of mesenchymal stromal cell on pediatric oxygenator performance and inflammatory response

Maeda¹,

Briggs

Datar³

et al. 2021

JTCVS Open

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“…29,59,62,63 The results of this study further support the ntMSC as an attractive candidate for cell therapy given their superior proangiogenic properties. Patients with congenital heart disease who undergo cardiac surgery in the neonatal or early infancy periods are at risk of developing medical conditions secondary to defective perfusion or angiogenesis, such as capillary rarefaction from ventricular pressure overload, which can contribute to heart failure, [64][65][66] cerebral damage from complications of cardiopulmonary bypass and cardiac surgery, 67,68 and myocardial ischemia and eventual heart failure from coronary obstruction after surgery. 69 Conceivably, autologous MSCs can be isolated from discarded thymus tissue obtained during neonatal or infant cardiac surgery, expanded and cryopreserved in vitro, and then thawed and used when medically indicated.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific angiogenic and invasive properties of human neonatal thymus and bone MSCs: Role of SLIT3-ROBO1

Wang

Huang

Johnson

et al. 2020

Stem Cells Translational Medicine

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Although mesenchymal stem/stromal cells (MSCs) are being explored in numerous clinical trials as proangiogenic and proregenerative agents, the influence of tissue origin on the therapeutic qualities of these cells is poorly understood. Complicating the functional comparison of different types of MSCs are the confounding effects of donor age, genetic background, and health status of the donor. Leveraging a clinical setting where MSCs can be simultaneously isolated from discarded but healthy bone and thymus tissues from the same neonatal patients, thereby controlling for these confounding factors, we performed an in vitro and in vivo paired comparison of these cells. We found that both neonatal thymus (nt)MSCs and neonatal bone (nb)MSCs expressed different pericytic surface marker profiles. Further, ntMSCs were more potent in promoting angiogenesis in vitro and in vivo and they were also more motile and efficient at invading ECM in vitro. These functional differences were in part mediated by an increased ntMSC expression of SLIT3, a factor known to activate endothelial cells. Further, we discovered that SLIT3 stimulated MSC motility and fibrin gel invasion via ROBO1 in an autocrine fashion. Consistent with our findings in human MSCs, we found that SLIT3 and ROBO1 were expressed in the perivascular cells of the neonatal murine thymus gland and that global SLIT3 or ROBO1 deficiency resulted in decreased neonatal murine thymus gland vascular density. In conclusion, ntMSCs possess increased proangiogenic and invasive behaviors, which are in part mediated by the paracrine and autocrine effects of SLIT3.

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A comparative study of mouse bone marrow mesenchymal stem cells isolated using three easy‐to‐perform approaches

Han

Zhou

et al. 2022

FEBS Open Bio

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Mouse bone marrow mesenchymal stem cells (mBM‐MSCs) are important for preclinical tissue regeneration and repair studies. In the present study, we isolated mBM‐MSCs using three easy‐to‐perform methods (whole bone marrow‐adherent culture, density‐gradient centrifugation, and bone digestion), and then compared the morphology, proliferation, differentiation, and paracrine factor profiles of the isolated mBM‐MSCs. Of these three isolation methods, the bone digestion method resulted in the highest quantity of mBM‐MSCs with high growth potential and moderate differentiation. Conversely, the mBM‐MSCs isolated through the whole bone marrow‐adherent method exhibited the lowest potency for proliferation and differentiation. The differentially expressed factors between mBM‐MSCs were primarily those involved in immune responses. The highly expressed secreted factors included cytokines/members of the chemokine family, growth factors, and protein binding/proteinase activity. These findings provide a fundamental reference for development of MSC isolation methods.

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Impact of Mesenchymal Stromal Cell Delivery Through Cardiopulmonary Bypass on Postnatal Neurogenesis

Cited by 13 publications

References 39 publications

Influence of administration of mesenchymal stromal cell on pediatric oxygenator performance and inflammatory response

Influence of administration of mesenchymal stromal cell on pediatric oxygenator performance and inflammatory response

Tissue-specific angiogenic and invasive properties of human neonatal thymus and bone MSCs: Role of SLIT3-ROBO1

A comparative study of mouse bone marrow mesenchymal stem cells isolated using three easy‐to‐perform approaches

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