Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy

Trachtenberg, Barry; Velazquez, Darcy L.; Williams, Adam R.; McNiece, Ian; Fishman, Joel E.; Nguyen, Kim; Rouy, Didier; Altman, Peter; Schwarz, Richard P.; Mendizabal, Adam; Oskouei, Behzad; Byrnes, John; Soto, Victor; Tracy, Melissa; Zambrano, Juan P.; Heldman, Alan W.; Hare, Joshua M.

doi:10.1016/j.ahj.2010.11.024

Cited by 126 publications

(82 citation statements)

References 24 publications

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“…These mostly sterile disposable systems contain standard plastic surfaces. Static cultivation is widely used in research labs and many therapies and clinical trials have been developed with cells expanded this way [42]. However, these culture vessels offer a limited scale-up potential and little possibilities for process control and cannot be automated easily.…”

Section: Expansion Of Hmsc In Static Systemsmentioning

confidence: 99%

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

Cierpka

Elseberg

Niss³

et al. 2012

Chemie Ingenieur Technik

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Reactor concepts for human mesenchymal stem cell (hMSC) production are introduced. Thereby, special interest is laid on the realization of these concepts as disposables fulfilling the GMP and PAT requirements. The specialty of the hMSC production process is the cell itself being the product. This results in completely different process requirements compared to e.g. protein production in mammalian cells. Thus, great attention has to be given to the shear sensitivity of the cells. The cultivation and the harvest of the cells have to be very gentle to neither influence cell viability nor cell differentiability. Further, the production process should not cause any undesirable cell changes. For hMSC production, cell harvest is the main challenging process step. The reactor concepts should be suitable for hMSC production for clinical trials as ATMPs. Therefore, disposable systems are especially applicable. The review describes more detailed bone marrow-derived hMSC production in a disposable stirred tank reactor as promising reactor concept.

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Section: Expansion Of Hmsc In Static Systemsmentioning

confidence: 99%

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

Cierpka

Elseberg

Niss³

et al. 2012

Chemie Ingenieur Technik

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“…This requirement still poses a major obstacle for the achievement of successful clinical applications. MSCs are present at very low numbers in tissues despite the fact that they can be isolated from a wide variety of sources (Aust et al 2004;Pittenger et al 1999), and it is not possible to isolate the large numbers of MSCs required for clinical trials from a single donor for each therapy (Trachtenberg et al 2011; Dae Seong Kim and Young Jong Ko contributed equally to this work.…”

Section: Introductionmentioning

confidence: 99%

Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells

Kim

Lee

et al. 2016

Cell Stress and Chaperones

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Culture of mesenchymal stem cells (MSCs) under ambient conditions does not replicate the low oxygen environment of normal physiological or pathological states and can result in cellular impairment during culture. To overcome these limitations, we explored the effect of hypoxia (1 % O 2 ) on the biological characteristics of MSCs over the course of different culture periods. The following biological characteristics were examined in human bone marrow-derived MSCs cultured under hypoxia for 8 weeks: proliferation rate, morphology, cell size, senescence, immunophenotypic characteristics, and the expression levels of stemness-associated factors and cytokine and chemokine genes. MSCs cultured under hypoxia for approximately 2 weeks showed increased proliferation and viability. During long-term culture, hypoxia delayed phenotypic changes in MSCs, such as increased cell volume, altered morphology, and the expression of senescence-associated-β-gal, without altering their characteristic immunophenotypic characteristics. Furthermore, hypoxia increased the expression of stemness and chemokine-related genes, including OCT4 and CXCR7, and did not decrease the expression of KLF4, C-MYC, CCL2, CXCL9, CXCL10, and CXCR4 compared with levels in cells cultured under normoxia. In conclusion, low oxygen tension improved the biological characteristics of MSCs during ex vivo expansion. These data suggest that hypoxic culture could be a useful method for increasing the efficacy of MSC cell therapies.

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“…Risultati più incoraggianti (FE +8-12%) ma ancora incompleti provengono dallo studio di fase I SCIPIO [58], in cui ai pazienti sono state somministrate CSC prelevate dall'auricola destra e amplificate in vitro. Lo studio TAC-HFT [59], sebbene condotto su un campione ristretto, ha dimostrato la sicurezza dell'uso MSC e BMC e la loro efficacia nel prevenire eventi maggiori, ma solo di carattere tromboembolico. Sta per essere avviato un grande trial internazionale di fase III, lo studio BAMI, che valuterà l'efficacia a 3 anni del trattamento con BMC nel prevenire la morte e l'ospedalizzazione per causa cardiovascolari in pazienti che hanno avuto un IMA.…”

Section: Cellule Staminaliunclassified

Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure: Part I

Sirico

Salzano

Celentani

et al. 2015

Monaldi Arch Chest Dis

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RASSEGNA IntroduzioneGrazie ai recenti miglioramenti delle tecniche di riperfusione coronarica e della terapia farmacologica dell'IMA, negli ultimi anni si è verificato un considerevole aumento della sopravvivenza dei pazienti con questa patologia, anche nei casi più severi [1,2]. Contemporaneamente ciò ha determinato un aumento della morbilità nei pazienti sopravvissuti i quali, in un arco di tempo che va da pochi giorni a diversi mesi, spesso sviluppano disfunzione sistolica e/o diastolica di grado variabile, aritmie maggiori e sintomi da ICC. Questa evoluzione è dovuta al remodeling, un meccanismo fisiopatologico che è stato definito "l'espressione genomica secondaria a danno cardiaco risultante in cambiamenti molecolari, cellulari e interstiziali che si manifestano clinicamente come cambiamenti di dimensione, forma e funzione del cuore" [3]. Come si evince dalla definizione, il remodeling si verifica in seguito a danno cardiaco di qualunque tipo, sia acuto che cronico; tuttavia l'infarto del miocardio ne rappresenta senza dubbio la causa più frequente e pertanto la maggior parte delle ricerche sul remodeling sono state condotte su modelli post-ischemici. Nell'ICC sono numerosi gli studi che stanno cercando testare nuove ipotesi, basate su meccanismi fisiopatologici complementari a quelli classici, nel tentativo di identificare nuovi bersagli terapeutici [4]. Si pensi al modello ormono-metabolico, che da anni si è affacciato nel panorama della ricerca clinica [5,6], date le crescenti evidenze di una connessione molto stretta tre le alterazioni ormonali e il sistema cardiovascolare [7,8]. Tra questi, il remodeling post-infartuale è stato oggetto di studi da oltre un ventennio e, sebbene rimangano numerosi aspetti ampiamente sconosciuti, le scoperte effettuate hanno permesso di progettare e mettere in atto delle strategie terapeutiche volte a contrastare specifiche alterazioni cellulari e molecolari in modo da prevenire le suddette manifestazioni patologiche [9]; come spesso accade in numerose condizioni cliniche [10,11], diversi sono i bersagli cellulari coinvolti, basti pensare alle cellule infiammatorie, In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. In this review, we evaluate the results obtained from four new therapeutic strategies: in this part we evaluate gene therapy and novel aspect of stem cells therapy in remodeling; in the second part we wil...

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Cited by 126 publications

References 24 publications

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells

Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure: Part I

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