Cryopreserved mesenchymal stromal cell treatment is safe and feasible for severe dilated ischemic cardiomyopathy

Chin, S.; Poey, Alfred C.; Wong, Chee-Yin; Chang, Sau-Kong; Teh, William; Mohr, Teddric Jon; Cheong, Soon-Keng

doi:10.3109/14653240903313966

Cited by 44 publications

(36 citation statements)

References 26 publications

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“…This is mainly attributed to the potential of MSCs to differentiate into cells of the cardiovascular lineage and ability to repair damaged tissue without eliciting an immune response in the host (6). Both freshly isolated (30) and cryopreserved MSCs (5,8,17) are currently being used in clinics as well as in research laboratories. The present study was performed on cryopreserved MSCs derived from rat bone marrow.…”

Section: Discussionmentioning

confidence: 99%

“…In our earlier studies we observed that the ischemic region in the infarct heart of murine models could reach an oxygen level as low as 0.2% (4,25), which would imply that the survival and proliferation of transplanted stem cells in the infarct tissue would require the cells to adapt to very low oxygen tension in the infarct heart. Currently, in clinics as well as in research laboratories, freshly isolated (30) and cryopreserved MSCs (5,8,17) are being used for cell therapy. In this study using cryogenic rat MSCs, we have attempted to further examine hypoxic preconditioning at 0.5% oxygen concentration at different time periods of hypoxia and passage of MSCs in culture.…”

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confidence: 99%

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Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells

Chacko

Ahmed

Selvendiran

et al. 2010

American Journal of Physiology-Cell Physiology

174

114

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preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells. Am J Physiol Cell Physiol 299: C1562-C1570, 2010. First published September 22, 2010; doi:10.1152/ajpcell.00221.2010.-Stem cells transplanted to the ischemic myocardium usually encounter massive cell death within a few days of therapy. Hypoxic preconditioning (HPC) is currently employed as a strategy to prepare stem cells for increased survival and engraftment in the heart. However, HPC of stem cells has provided varying results, supposedly due to the differences in the oxygen concentration, duration of exposure, and passage conditions. In the present study, we determined the effect of HPC on rat mesenchymal stem cells (MSCs) exposed to 0.5% oxygen concentration for 24, 48, or 72 h. We evaluated the expression of prosurvival, proangiogenic, and functional markers such as hypoxia-inducible factor-1␣, VEGF, phosphorylated Akt, survivin, p21, cytochrome c, caspase-3, caspase-7, CXCR4, and c-Met. MSCs exposed to 24-h hypoxia showed reduced apoptosis on being subjected to severe hypoxic conditions. They also had significantly higher levels of prosurvival, proangiogenic, and prodifferentiation proteins when compared with longer exposure (72 h). Cells taken directly from the cryopreserved state did not respond effectively to the 24-h HPC as those that were cultured under normoxia before HPC. Cells cultured under normoxia before HPC showed decreased apoptosis, enhanced expression of connexin-43, cardiac myosin heavy chain, and CD31. The preconditioned cells were able to differentiate into the cardiovascular lineage. The results suggest that MSCs cultured under normoxia before 24-h HPC are in a state of optimal expression of prosurvival, proangiogenic, and functional proteins that may increase the survival and engraftment in the infarct heart. These results could provide further insights into optimal preparation of MSCs which would greatly influence the effectiveness of cell therapy in vivo. myocardial infarction; cell therapy THE OXYGEN CONCENTRATION in the microenvironment of stem cells plays an important role in controlling stem cell potency, proliferation, and differentiation ability (1,26,28). Stem cells that are normally cultured at ambient air in an in vitro environment differ in their exposure to the concentration of oxygen, compared with their natural physiological niches where they reside and function (7, 9). During cell transplantation procedures to treat conditions such as myocardial infarction (MI), the cultured stem cells encounter a sudden shortage in oxygen availability when transplanted into an ischemic heart tissue. A growing body of evidence attributes failure of stem cell therapy to the extensive loss of transplanted stem cells upon introducing them to such a harsh ischemic environment, which is high in inflammation factors and free radicals generated by oxidative stress (14, 38). Varying the oxygen exposure level while culturing the stem cells may play a major role in determining the survival of...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells

Chacko

Ahmed

Selvendiran

et al. 2010

American Journal of Physiology-Cell Physiology

174

114

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“…18,19 On the other hand, cryopreservation does not alter the surface marker profiles and osteogenic potential of BM-MSCs or compromise the therapeutic effects on cardiac function after direct intramyocardial injection. 20,21 Difference in donors or the cultivation period after cell thawing might affect the characteristics of MSCs. 18,22 In our study, MSCs that were isolated from cryopreserved UCB cells showed a similar morphology, surface marker expression profile as BM-MSCs, and had capability to differentiate into osteogenic, adipogenic, and chondrogenic cells.…”

Section: Discussionmentioning

confidence: 99%

Isolation of mesenchymal stromal/stem cells from cryopreserved umbilical cord blood cells

Fujii

Miura

Iwasa

et al. 2017

J Clin Exp Hematopathol

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JC EH lin xp ematopathol Original Article INTRODUCTIONCell therapy using human mesenchymal stromal/stem cells (MSCs) has been extensively explored for the treatment of a variety of diseases based on their multiple biological and therapeutic effects.1 An off-the-shelf allogeneic bone marrow (BM)-derived MSC product is currently available in the clinic for the treatment of the intractable acute graft-versushost disease after hematopoietic stem cell transplantation (HSCT). 2,3 BM is the most commonly used source of MSCs. 4 However, invasive procedures are required to obtain BM cells from donors. Although other sources of MSCs that can be obtained without invasive treatments have been sought, including expulsed placenta and exfoliated teeth, complex procedures with enzymatic digestion are necessary to prepare cells from these tissues. 5,6 The demand for allogeneic MSCs is expected to increase in the future; therefore, appropriate sources of MSCs that can be alternatives to BM need to be explored for the further development of MSCbased therapy.In a previous study, we demonstrated that MSCs can be isolated from freshly donated umbilical cord blood (UCB) units that do not qualify for the Japanese banking system as a hematopoietic stem cell (HSC) source because of their small volume.7 UCB has advantages over other tissues because it can be obtained from donors without invasive procedures, and a simple adhesion method without complex procedures can be used to isolate MSCs. In addition, infrastructure for processing and cryopreserving UCB cells is established in the banking system for HSCT in Japan. More importantly, about 90% of donated UCB units are discarded because they do not meet the requirements for an HSC source in terms of volume and/or cell number. 8 We have further extended our investigation of the availability of such UCB units as a Umbilical cord blood (UCB) has advantages over other tissues because it can be obtained without an invasive procedure and complex processing. We explored the availability of cryopreserved UCB cells as a source of mesenchymal stromal/stem cells (MSCs). MSCs were successfully isolated from six of 30 UCB units (median volume, 34.0 mL; median nucleated cell number, 4.4×10 8 ) that were processed and cryopreserved using CP-1/human serum albumin. This isolation rate was lower than that (57%) from non-cryopreserved UCB cells. The number of nucleated cells before and after hydroxyethyl starch separation, UCB unit volume, and cell viability after thawing did not significantly differ between UCB units from which MSCs were successfully isolated and those from which they were not. When CryoSure-DEX40 was used as a cryoprotectant, MSCs were isolated from two of ten UCB units. Logistic regression analysis demonstrated that the cryopreservation method was not significantly associated with the success of MSC isolation. The isolated MSCs had a similar morphology and surface marker expression profile as bone marrow-derived MSCs and were able to differentiate into osteogenic, adipogenic, and chondro...

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“…Saw an increase in muscle mass 156.2 to 181.4 during the first year but decreased to 179.4 in the second year after cell therapy, indicating that the ideal for the regeneration of muscle mass period is the first year post treatment and these results are statistically significant when compared with placebo. Another group showed a significant improvement in cardiac function and volume, resolution of healing and increased wall thickness for severe ischemic dilated cardiomyopathy patients with cardiac magnetic resonance imaging at 6 months of infusion of bone marrow stem cells in relation to baseline [23].…”

Section: Citationmentioning

confidence: 99%

“…Tremendous excitement and controversy have seen in the fields of stem cell biology and cardiac regeneration [22]. Studies in ischemic heart disease demonstrated that stem cells obtained from various sources, including bone marrow, can contribute indirectly to cardiac regeneration [23][24][25][26], and indicated the potential use of stem cell therapy in other cardiomyopathies [27,28].…”

Section: Introductionmentioning

confidence: 99%

Cardiomyopathy and Cell Therapy: Ejection Fraction Improvement and Cardiac Muscle Mass Increasing, after a Year of Bone Marrow Stem Cells Transplantation, by Magnetic Resonance Image

Grzeco¹

2013

J Stem Cell Res Ther

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The idiopathic dilated cardiomyopathy (IDC) is one of the major public health problems in the western world. Patients with IDC in functional class IV (New York Health Association -NYHA), even after therapeutic optimization, have high mortality. Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases and several positive effects were assigned to cell therapy in cardiomyopathy. The aim of this study was identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy patients (IDC) who were treated by transplantation of autologous bone marrow mononuclear cells (BMMC). Intracoronary injections of autologous BMMC were performed in eight patients with severe ventricle dysfunction (mean of left ventricle ejection fraction -LEVF=20.03%), cardiac mass muscle around 156.2 g and NYHA between III and IV grades, other 8 IDC patients received placebo. The IDCs were followed -up for one and two years, by magnetic resonance imaging (MRI). The results after one year showed significant improvement in LVEF (mean=181.4) and muscle mass increasing (mean=181.4 g), after two years the LVEF continued improving, reaching a mean of 32.69% and the cardiac muscle mass kept stable (mean=179.4 g). Excepted for one patient, all the other had improvement in the NYHA functional class. The placebo group did not show any improvement. We believe that BMMC implant may be a beneficial therapeutic option for IDC patients.

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Cryopreserved mesenchymal stromal cell treatment is safe and feasible for severe dilated ischemic cardiomyopathy

Cited by 44 publications

References 26 publications

Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells

Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells

Isolation of mesenchymal stromal/stem cells from cryopreserved umbilical cord blood cells

Cardiomyopathy and Cell Therapy: Ejection Fraction Improvement and Cardiac Muscle Mass Increasing, after a Year of Bone Marrow Stem Cells Transplantation, by Magnetic Resonance Image

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