Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

Figures & data

Table 1. Various cell sources used in regenerative therapy

Cell sources
Endothelial progenitor cells^7
Bone marrow^8^,^9
Adipose tissue^10
Placenta and umbilical cord^11
Human amniotic fluid^12
Dental pulp^13
Skeletal muscle^14
Fetal cardiomyocytes^15^,^16
Skeletal myoblasts^17^,^18
Mesenchymal stem cells^19
Smooth muscle cells^20
Crude bone marrow^21
Fibroblasts^22^,^23
Cloned cells^24

Figure 1. Influence of calcium on the functioning of cardiomyocyte.

Table 2. Local functions of various cytokine-mediated therapy

Cytokine	Local Function
G-CSF	Stimulation of myeloid progenitor cells Mobilization of hemopoietic stem cells Healing and repair
EPO	Erythrocyte survival and differentiation Vascular auto regulation Prevention of apoptosis and inflammation
SDF-1	Stimulates hematopoietic and endothelial progenitors Activates mesenchymal stem cells Neovascularization
TNF-α	Downregulate myocyte contractility
IL-6	Reduction of systolic cytosolic [Ca^2+]

Figure 2. Nature and role of various growth factors in regenerative therapy.

Figure 3. The general procedure for cardiac tissue engineering.

Table 3. Scaffolds materials used in tissue engineering

Synthetic scaffolds materials	Natural scaffold materials
Poly lactic acid^92	Fibrin glue^96^,^97
Poly glycolic acid^92	Gelatin^98
Hydroxyethyl methacrylate (HEMA)^93	Collagen^99^,^100
Methyl methacrylate (MMA)^93	Alginate^101^,^102
Poly propylene fumarate (PPF)^94	Chitosan^103
Poly(dioxanone)^95	Hyaluronoc acid^104
Poly(e-caprolactone)^95	Mussel proteins^105
Poly(trimethylene carbonate) copolymers^96	Elastin^106

Figure 4. Essential characteristics of an ideal tissue engineering scaffold.

Ryu JH, Kim IK, Cho SW, Cho MC, Hwang KK, Piao H, et al. Implantation of bone marrow mononuclear cells using injectable fibrin matrix enhances neovascularization in infarcted myocardium. Biomaterials 2005; 26:319 - 26; http://dx.doi.org/10.1016/j.biomaterials.2004.02.058; PMID: 15262474

 PubMed Web of Science ®Google Scholar

Kellar RS, Landeen LK, Shepherd BR, Naughton GK, Ratcliffe A, Williams SK. Scaffold-based three-dimensional human fibroblast culture provides a structural matrix that supports angiogenesis in infarcted heart tissue. Circulation 2001; 104:2063 - 8; http://dx.doi.org/10.1161/hc4201.097192; PMID: 11673347

 PubMed Web of Science ®Google Scholar

Shimizu T. Myocardial Tissue Engineering. In: Eberli D, ed. Tissue Engineering for Tissue and Organ Regeneration. InTech, 2011.

 Google Scholar

Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968; 6:230 - 47; http://dx.doi.org/10.1097/00007890-196803000-00009; PMID: 5654088

 PubMed Web of Science ®Google Scholar

Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114:763 - 76; http://dx.doi.org/10.1016/S0092-8674(03)00687-1; PMID: 14505575

 PubMed Web of Science ®Google Scholar

Gandia C, Armiñan A, Garci´a-Verdugo JM, Lledo´ E, Ruiz A, Miñana MD, et al. Human dental pulp stem cells improve left ventricular function, induce angiogenesis, and reduce infarct size in rats with acute myocardial infarction. Stem Cells 2008; 26:638 - 45; http://dx.doi.org/10.1634/stemcells.2007-0484; PMID: 18079433

 PubMed Web of Science ®Google Scholar

Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 2010; 142:375 - 86; http://dx.doi.org/10.1016/j.cell.2010.07.002; PMID: 20691899

 PubMed Web of Science ®Google Scholar

Seale P, Asakura A, Rudnicki MA. The potential of muscle stem cells. Dev Cell 2001; 1:333 - 42; http://dx.doi.org/10.1016/S1534-5807(01)00049-1; PMID: 11702945

 PubMed Web of Science ®Google Scholar

Li RK, Jia ZQ, Weisel RD, Mickle DA, Choi A, Yau TM. Survival and function of bioengineered cardiac grafts. Circulation 1999; 100:II63 - 9; http://dx.doi.org/10.1161/01.CIR.100.suppl_2.II-63; PMID: 10567280

 PubMed Web of Science ®Google Scholar

Leor J, Aboulafia-Etzion S, Dar A, Shapiro L, Barbash IM, Battler A, et al. Bioengineered cardiac grafts: A new approach to repair the infarcted myocardium?. Circulation 2000; 102:III56 - 61; http://dx.doi.org/10.1161/01.CIR.102.suppl3.III-56; PMID: 11082363

 PubMed Web of Science ®Google Scholar

Kamelger FS, Marksteiner R, Margreiter E, Klima G, Wechselberger G, Hering S, et al. A comparative study of three different biomaterials in the engineering of skeletal muscle using a rat animal model. Biomaterials 2004; 25:1649 - 55; http://dx.doi.org/10.1016/S0142-9612(03)00520-9; PMID: 14697866

 PubMed Web of Science ®Google Scholar

Li RK. Cell transplantation to improve heart function: cell or matrix. Yonsei Med J 2004; 45:S72 - 3

 Google Scholar

Krupnick AS, Kreisel D, Szeto WY, Popma SH, Rosengard BR. A murine model of left ventricular tissue engineering. J Heart Lung Transplant 2001; 20:197 - 8; http://dx.doi.org/10.1016/S1053-2498(00)00417-4; PMID: 11250343

 PubMedGoogle Scholar

Matsubayashi K, Fedak PW, Mickle DA, Weisel RD, Ozawa T, Li RK. Improved left ventricular aneurysm repair with bioengineered vascular smooth muscle grafts. Circulation 2003; 108:Suppl 1 II219 - 25; http://dx.doi.org/10.1161/01.cir.0000087450.34497.9a; PMID: 12970236

 PubMed Web of Science ®Google Scholar

Wu X, Rabkin-Aikawa E, Guleserian KJ, Perry TE, Masuda Y, Sutherland FWH, et al. Tissue-engineered microvessels on three-dimensional biodegradable scaffolds using human endothelial progenitor cells. Am J Physiol Heart Circ Physiol 2004; 287:H480 - 7; http://dx.doi.org/10.1152/ajpheart.01232.2003; PMID: 15277191

 PubMed Web of Science ®Google Scholar

Li RK, Yau TM, Weisel RD, Mickle DA, Sakai T, Choi A, et al. Construction of a bioengineered cardiac graft. J Thorac Cardiovasc Surg 2000; 119:368 - 75; http://dx.doi.org/10.1016/S0022-5223(00)70193-0; PMID: 10649213

 PubMed Web of Science ®Google Scholar

Lanza R, Moore MA, Wakayama T, Perry AC, Shieh JH, Hendrikx J, et al. Regeneration of the infarcted heart with stem cells derived by nuclear transplantation. Circ Res 2004; 94:820 - 7; http://dx.doi.org/10.1161/01.RES.0000120863.53562.DF; PMID: 14764454

 PubMed Web of Science ®Google Scholar

Lee MS, Makkar RR. Stem-cell transplantation in myocardial infarction: a status report. Ann Intern Med 2004; 140:729 - 37; PMID: 15126257

 PubMed Web of Science ®Google Scholar

Kim BS, Mooney DJ. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol 1998; 16:224 - 30; http://dx.doi.org/10.1016/S0167-7799(98)01191-3; PMID: 9621462

 PubMed Web of Science ®Google Scholar

Ehrbar M, Djonov VG, Schnell C, Tschanz SA, Martiny-Baron G, Schenk U, et al. Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth. Circ Res 2004; 94:1124 - 32; http://dx.doi.org/10.1161/01.RES.0000126411.29641.08; PMID: 15044320

 PubMed Web of Science ®Google Scholar

Zisch AH, Schenk U, Schense JC, Sakiyama-Elbert SE, Hubbell JA. Covalently conjugated VEGF--fibrin matrices for endothelialization. J Control Release 2001; 72:101 - 13; http://dx.doi.org/10.1016/S0168-3659(01)00266-8; PMID: 11389989

 PubMed Web of Science ®Google Scholar

Rosellini E, Cristallini C, Barbani N, Vozzi G, Giusti P. Preparation and characterization of alginate/gelatin blend films for cardiac tissue engineering. J Biomed Mater Res A 2009; 91:447 - 53; http://dx.doi.org/10.1002/jbm.a.32216; PMID: 18985761

 PubMed Web of Science ®Google Scholar

van Wachem PB, Hogt AH, Beugeling T, Feijen J, Bantjes A, Detmers JP, et al. Adhesion of cultured human endothelial cells onto methacrylate polymers with varying surface wettability and charge. Biomaterials 1987; 8:323 - 8; http://dx.doi.org/10.1016/0142-9612(87)90001-9; PMID: 3676418

 PubMed Web of Science ®Google Scholar

Steffens GC, Yao C, Pre´vel P, Markowicz M, Schenck P, Noah EM, et al. Modulation of angiogenic potential of collagen matrices by covalent incorporation of heparin and loading with vascular endothelial growth factor. Tissue Eng 2004; 10:1502 - 9; PMID: 15588409

 PubMedGoogle Scholar

Kanematsu A, Yamamoto S, Ozeki M, Noguchi T, Kanatani I, Ogawa O, et al. Collagenous matrices as release carriers of exogenous growth factors. Biomaterials 2004; 25:4513 - 20; http://dx.doi.org/10.1016/j.biomaterials.2003.11.035; PMID: 15046942

 PubMed Web of Science ®Google Scholar

Rowley JA, Madlambayan G, Mooney DJ. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 1999; 20:45 - 53; http://dx.doi.org/10.1016/S0142-9612(98)00107-0; PMID: 9916770

 PubMed Web of Science ®Google Scholar

Rowley JA, Mooney DJ. Alginate type and RGD density control myoblast phenotype. J Biomed Mater Res 2002; 60:217 - 23; http://dx.doi.org/10.1002/jbm.1287; PMID: 11857427

 PubMed Web of Science ®Google Scholar

Krishna L, Jayabalan M. Synthesis and characterization of biodegradable poly (ethylene glycol) and poly (caprolactone diol) end capped poly (propylene fumarate) cross linked amphiphilic hydrogel as tissue engineering scaffold material. J Mater Sci Mater Med 2009; 20:Suppl 1 S115 - 22; http://dx.doi.org/10.1007/s10856-008-3493-3; PMID: 18584124

 PubMedGoogle Scholar

Li Z, Guan J. Hydrogels for Cardiac Tissue Engineering. Polymers 2011; 3:740 - 61; http://dx.doi.org/10.3390/polym3020740

 Web of Science ®Google Scholar

Barrows TH. Degradable implant materials: a review of synthetic absorbable polymers and their applications. Clin Mater 1986; 1:233 - 57; http://dx.doi.org/10.1016/S0267-6605(86)80015-4

 Google Scholar

Di Felice V, De Luca A, Serradifalco C, Di Marco P, Verin L, Motta A, et al. Adult stem cells, scaffolds for in vivo and in vitro myocardial tissue engineering. Ital J Anat Embryol 2010; 115:65 - 9; PMID: 21072992

 PubMedGoogle Scholar

Dalsin JL, Hu BH, Lee BP, Messersmith PB. Mussel adhesive protein mimetic polymers for the preparation of nonfouling surfaces. J Am Chem Soc 2003; 125:4253 - 8; http://dx.doi.org/10.1021/ja0284963; PMID: 12670247

 PubMed Web of Science ®Google Scholar

Lu Q, Ganesan K, Simionescu DT, Vyavahare NR. Novel porous aortic elastin and collagen scaffolds for tissue engineering. Biomaterials 2004; 25:5227 - 37; http://dx.doi.org/10.1016/j.biomaterials.2003.12.019; PMID: 15110474

 PubMed Web of Science ®Google Scholar