The Immature Heart: The Roles of Bone Marrow Stromal Stem Cells in Growth and Myocardial Repair

Studies have shown that adult bone marrow derived stem cells (MSCs) can participate in repair of myocardial injury in adult hearts, as well as in cardiac growth during fetal development in utero. Yet, no studies have evaluated the role of MSCs with respect to normal growth or tissue repair in immature hearts after birth. The present study examines whether MSCs may participate in the myocardial growth and injury in the post-natal immature hearts. MSCs were isolated from adult Lewis rats and labeled with Lac-Z gene using retroviral vectors. These MSCs were injected systemically into groups of neonatal (NB=2days-old), immature (B=30days-old) and adult (A=>3months-old) isogeneic Lewis rats. Additionally, left coronary artery ligation was carried out in subgroups of immature (BL) and adult (AL) rats one week after MSCs injection. The hearts were harvested serially from 2-days to 6-weeks, stained with X-Gal for labeled MSCs. Cardiomyocyte phenotypic expression was evaluated by immunohistological staining for Troponin I-C and Connexin-43. Labeled MSCs were found to home into the bone marrow in all rats of different developmental stages. They could be recruited from bone marrow into the infarcted site of myocardium only in groups AL and BL. They were also capable of differentiating into cardiomyocyte phenotype after myocardial injury. In contrast to that reported in the developing fetus, MSCs did not appear to contribute to the growth of non-injured hearts after birth. However, they can be recruited from the bone marrow and regenerate damaged myocardium both in the adult and in the immature hearts

Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

<p>Abstract</p> <p>Purpose</p> <p>Bisphosphonate - related osteonecrosis of the JAW (BRONJ) is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient.</p> <p>Methods</p> <p>Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque^®centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ.</p> <p>Results</p> <p>A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0) was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ.</p> <p>Conclusion</p> <p>To our knowledge this is the first case of BRONJ successfully treated with autologous stem cells transplantation with a complete response.</p

Bone marrow stromal cells in the tissue repair process following myocardial infarction

Marrow stromal cells (MSCs) are pluripotent stem cells which may participate in the repair of damaged organs. We tested the hypothesis that MSCs can be recruited to the heart upon myocardial infarction, and play pathophysiological roles in the subsequent healing and adaptation process. An animal model was created with labeled MSCs in its bone marrow and then a myocardial infarction produced. Donor MSCs from isogenic Lewis rats were harvested, multiplied in culture and labelled. Labelled cells were intravenously injected into the recipient rats and one week later upon the engraftment of these labelled MSCs within the bone marrow, rats underwent a coronary artery ligation or sham operation. The hearts were removed at various time points and the presence of labelled cells in the heart was confirmed and their phenotypes identified. We confirmed the presence of labelled cells in the rat bone marrows and the presence of labelled cells in the infarcted myocardium at all time points studied, but not in the normal hearts. There was evidence for myogenic differentiation with some labelled cells expressing smooth muscle/myofibroblast phenotypes and appearing to participate in vasculogenesis. Our evidence is consistent with the hypothesis that myocardial infarction may send a signal to recruit MSCs to the injured heart, where they undergo milieu-dependent differentiation. The ability of these cells to express various phenotypes may allow them to participate in the pathophysiology of post-infarct remodeling and angiogenesis. Therapeutic implantation of MSCs thus may further enhance such effects

Aortic valve grafts in the rat: evidence for rejection.

OBJECTIVE:The histopathologic changes of fresh rat aortic valve allografts over time and the effect of cryopreservation were examined.METHODS:Fifty-six syngeneic and allogeneic rat aortic valves were transplanted, either fresh or after cryopreservation, and then at different time points they were explanted and histologically examined in a blinded fashion.RESULTS:Histopathologic changes in the first week are similar in syngeneic and allogeneic grafts. Fresh syngeneic grafts and leaflets retained normal structure up to 56 days. Allogeneic grafts showed retrovalvular thrombus formation with leaflet ghosts and neointimal proliferation. Cryopreservation did not alter this process.CONCLUSIONS:Cardiac allograft valves in the rat model undergo changes that are characteristic of cell-mediated rejection and lead to valve failure

The Combined Use of Extracorporeal Life Support and the

There is a very limited published material about experience with long-term pediatric mechanical circulatory support as a bridge to heart transplant. We report on a 2-year-old, 12 kg boy admitted with 2-week history of low-grade fever, ear pain, pulmonary edema, and congestive heart failure. Trans-thoracic echocardiography confirmed severe myocardial dysfunction with a left ventricular ejection fraction of 0.20 and percentage shortening of 13. After 2 days of ventilatory and inotropic support, the patient continued to deteriorate and subsequently required femoro–femoral extracorporeal life support (ECLS). This was later complicated by a progressive coagulopathy and massive bleeding. On day 17, a pulsatile pediatric paracorporeal biventricular assist device (VAD) (Berlin Heart) was implanted. The patient’s condition improved significantly with all coagulopathies corrected, and the patient was extubated 21 days later. After 109 days of bi-VAD support, the patient was successfully transplanted and discharged home 45 days post transplant. Our early experience with initial ECLS bridge to VAD and subsequently to transplant was encouraging. It allowed for additional time to select the ideal organ donor and optimize the recipient’s comorbid condition and multiorgan failure. VAD provides an additional armamentarium of circulatory support in pediatric patients with severe heart failure

Intermediate-term Outcomes Following a Case Series of Reoperations for Medtronic Freestyle Stentless Aortic Valves

Background: Data are limited on long-term outcomes in patients who have undergone a reoperation following failure of a stentless aortic valve. Methods: Between 2006 and 2016, a retrospective analysis was performed on 24 patients who underwent open aortic valve replacement surgery for a failed stentless aortic valve prosthesis at Health Sciences North, Sudbury, Ontario, Canada. The primary outcome was a low mortality rate from cardiac-related deaths after 5 years. Results: All patients underwent insertion of a Medtronic Freestyle bioprosthesis (Minneapolis, MN) implanted using the modified subcoronary technique for their initial operation. The interval from the first operation to the stentless redo surgery ranged from 6 to 13 years. Aortic valve reoperation was performed for structural valve deterioration in 96% (n = 23) of the cases. Reoperations involved a removal of the stented valve leaflets and standard aortic valve replacement within the stentless casing in 20% (n = 5) of the cases, with the remaining cases requiring complete removal of the stentless prosthesis and aortic valve replacement. In those in whom a complete removal of the stentless valve was possible (n = 19), no disruption of the native aortic root occurred, with a 0% rate of conversion to a Bentall procedure. No intraoperative mortality occurred. The 30-day and 10-year operative mortality rates were 4% and 16%, respectively. Conclusions: Redo surgery for failing stentless valves can be done with relatively low risk and with acceptable long-term outcomes without resorting to root-replacement techniques. Résumé: Contexte: Il existe peu de données sur les résultats à long terme chez les patients qui ont subi une réintervention chirurgicale après une défaillance d’une valve aortique sans armature (stentless) ayant été implantée. Méthodologie: Nous avons réalisé une analyse rétrospective, de 2006 à 2016, auprès de 24 patients ayant subi une intervention chirurgicale invasive de remplacement de valve aortique en raison de la défaillance d’une prothèse aortique sans armature à l’hôpital Health Sciences North situé à Sudbury (Ontario), au Canada. Le paramètre principal d’évaluation était un faible taux de mortalité d’origine cardiaque après 5 ans. Résultats: Tous les patients avaient initialement subi l’implantation d’une bioprothèse Medtronic Freestyle (Minneapolis, Minnesota) par la technique sous-coronaire modifiée. La période écoulée entre la première intervention chirurgicale et la réintervention au niveau de la valve sans armature allait de 6 à 13 ans. Dans 96 % des cas (n = 23), la réintervention était réalisée en raison d’une détérioration de structure de la valve aortique. La réintervention avait consisté en un retrait des cuspides avec armature et un remplacement de valve aortique standard dans la membrane sans armature dans 20 % des cas (n = 5) et un retrait complet de la prothèse sans armature avec remplacement de la valve aortique avait été nécessaire dans les autres cas. Chez les patients pour qui le retrait complet de la valve sans armature a été possible (n = 19), aucune déchirure de la racine aortique native n’est survenue et le taux de passage à une intervention de Bentall était de 0 %. Aucun décès peropératoire n’est survenu. Les taux de mortalité à 30 jours et à 10 ans s’élevaient à 4 % et à 16 %, respectivement. Conclusions: La réintervention chirurgicale après la défaillance d’une valve aortique sans armature peut être réalisée avec des risques re-lativement faibles et des résultats à long terme acceptables sans avoir recours à des techniques de remplacement de la racine aortique

Mimicking Native Extracellular Matrix with Phytic Acid-Crosslinked Protein Nanofibers for Cardiac Tissue Engineering

10.1002/mabi.201200391Macromolecular Bioscience133366-375MBAI