Surgical treatment for heart failure: cell-based therapy with engineered tissue

Lancaster, Jordan J.; Koevary, Jen Watson; Chinyere, Ikeotunye Royal; Daugherty, Sherry; Fox, Kenneth A.; Goldman, Steven

doi:10.20517/2574-1209.2019.16

Cited by 2 publications

(9 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because we are dealing with a xenograft transplant, i.e., putting human fibroblasts and human cardiomyocytes into an immune-competent rat, we studied the immune responses of the TE patch in vivo with the rats receiving no immune suppression. We showed that our TE patch partially reversed LV remodeling [18] . This work documented the therapeutic benefits of our bioengineered patch in rats with CHF.…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 64%

“…The important findings of this study were that the TE patchtreated rats decreased LV-end diastolic pressure and the time constant of LV relaxation (Tau), increased anterior wall thickness in diastole, improved echocardiographic-derived indices of diastolic function E/e' [ratio of early peak flow velocity to early peak LV velocity] and e'/a' [ratio of early to late peak LV velocity]. The graft-treated rats have a pressure/volume filling curve shifted back towards SHAM and a lower LV enddiastolic operating volume, consistent with reversal of maladaptive remodeling related to compliance [16][17][18] [Figures 2-4].…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 78%

“…All rats remained in sinus rhythm with synchronized contraction through the patch area documented by transthoracic echocardiography. Transplanted hiPSC-CMs were observed at 7 days but not at 21 days after implantation; despite this LV function improved [16,18] . The patch increased gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction a-1 protein (connexin 43), β-myosin heavy chain 7, and insulin growth factor-1 expression in the infarcted heart after treatment [16] .…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 92%

“…Further, this reduces potential concerns of the effect of immunosuppression on the implanted cells. Importantly, in our pre-clinical studies completed to date, data to support safety and efficacy were demonstrated in immune-competent animals receiving no immune suppression [16,18] .…”

Section: Inclusion Criteria Exclusion Criteriamentioning

confidence: 99%

See 3 more Smart Citations

Perspective on the development of a bioengineered patch to treat heart failure: rationale and proposed design of phase I clinical trial

Goldman¹,

Traverse²,

Zile³

et al. 2022

Vessel Plus

Self Cite

View full text Add to dashboard Cite

This perspective focuses on the development of tissue engineered (TE) cell-based therapies to treat left ventricular (LV) dysfunction and chronic heart failure (CHF). The development of induced pluripotent stem cells enabled investigators to seed or co-culture human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) alone and in combination with other cells onto bioengineered scaffolds applied to the epicardial surface of the damaged left ventricle. Using our work as an example, we show how a xenograft implant of a bioengineered scaffold embedded with human neonatal fibroblasts and seeded with hiPSC-CMs partially reversed maladaptive LV remodeling and improved LV systolic/diastolic function in an immune-competent rat model of CHF. The fibroblasts lay down an extracellular matrix and secrete growth factors that increase myocardial blood flow. This approach provides an improved cell payload that covers a larger area of the damaged left ventricle as opposed to direct cell injections into the heart or down the coronary arteries. These studies combined with ongoing studies in immune-competent Yucatan mini swine treated with the same xenograft led to the preliminary design of a proposed Phase I clinical trial that will be presented to the Federal Drug Administration. For the proposed Phase I clinical, this TE patch will be implanted onto the epicardial surface of non-immunosuppressed patients undergoing elective Coronary Artery Bypass Grafting with Ejection Fractions ≥ 20% and ≤ 45%. The primary endpoints will be adverse events/severe adverse events associated with placing the TE patch on the heart. While Phase I trials are primarily safety trials, this proposed trial is designed to obtain some potential efficacy endpoints to help with the design of future Phase II/III clinical trials. These endpoints include changes in LV remodeling that were seen in the pre-clinical animal models as well as including endpoints that focus on patient well-being.

show abstract

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 64%

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 78%

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 92%

Section: Inclusion Criteria Exclusion Criteriamentioning

confidence: 99%

See 2 more Smart Citations

Perspective on the development of a bioengineered patch to treat heart failure: rationale and proposed design of phase I clinical trial

Goldman¹,

Traverse²,

Zile³

et al. 2022

Vessel Plus

Self Cite

View full text Add to dashboard Cite

show abstract

“…While management of the HF patients continues to improve, there remains a need for new therapeutic options that directly mitigate disease progression. The development of human induced pluripotent stem cells (hiPSCs) provides an opportunity to utilize novel cell types in engineered tissue platforms for regenerative therapy [ 3 , 4 ]. For the first time, hiPSC-derived cardiomyocytes (hiPSC-CMs) are being evaluated in HF patients at Osaka University, where cardiothoracic surgeons are implanting hiPSC-CM sheets on the epicardium ( NCT04696328 ).…”

Section: Introductionmentioning

confidence: 99%

Epicardially Placed Bioengineered Cardiomyocyte Xenograft in Immune-Competent Rat Model of Heart Failure

Chinyere

Bradley

Uhlorn

et al. 2021

Stem Cells International

Self Cite

View full text Add to dashboard Cite

Background. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are under preclinical investigation as a cell-based therapy for heart failure post-myocardial infarction. In a previous study, tissue-engineered cardiac grafts were found to improve hosts’ cardiac electrical and mechanical functions. However, the durability of effect, immune response, and in vitro properties of the tissue graft remained uncharacterized. This present study is aimed at confirming the graft therapeutic efficacy in an immune-competent chronic heart failure (CHF) model and providing evaluation of the in vitro properties of the tissue graft. Methods. hiPSC-CMs and human dermal fibroblasts were cultured into a synthetic bioabsorbable scaffold. The engineered grafts underwent epicardial implantation in infarcted immune-competent male Sprague-Dawley rats. Plasma samples were collected throughout the study to quantify antibody titers. At the study endpoint, all cohorts underwent echocardiographic, hemodynamic, electrophysiologic, and histopathologic assessments. Results. The epicardially placed tissue graft therapy improved ( p < 0.05 ) in vivo and ex vivo cardiac function compared to the untreated CHF cohort. Total IgM and IgG increased for both the untreated and graft-treated CHF cohorts. An immune response to the grafts was detected after seven days in graft-treated CHF rats only. In vitro, engineered grafts exhibited responsiveness to beta-adrenergic receptor agonism/antagonism and SERCA inhibition and elicited complex molecular profiles. Conclusions. This hiPSC-CM-derived cardiac graft improved systolic and diastolic cardiac function in immune-competent CHF rats. The improvements were detectable at seven weeks post-graft implantation despite an antibody response beginning at week one and peaking at week three. This suggests that non-integrating cell-based therapy delivered by a bioengineered tissue graft for ischemic cardiomyopathy is a viable treatment option.

show abstract

Surgical treatment for heart failure: cell-based therapy with engineered tissue

Cited by 2 publications

References 53 publications

Perspective on the development of a bioengineered patch to treat heart failure: rationale and proposed design of phase I clinical trial

Perspective on the development of a bioengineered patch to treat heart failure: rationale and proposed design of phase I clinical trial

Epicardially Placed Bioengineered Cardiomyocyte Xenograft in Immune-Competent Rat Model of Heart Failure

Contact Info

Product

Resources

About