Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction.
Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability "in vitro" and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78+/-41x10(6) per patient) were intracoronarily transplanted 13.5+/-5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11+/-5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.
Fernández-Avilés
Francisco
F
Instituto de Ciencias del Corazón (ICICOR), Hospital Clínico Universitario. C/O Ramón y Cajal 3, E-47005-Valladolid, Spain. faviles@secardiologia.es
San Román
José Alberto
JA
García-Frade
Javier
J
Fernández
María Eugenia
ME
Peñarrubia
María Jesús
MJ
de la Fuente
Luis
L
Gómez-Bueno
Manuel
M
Cantalapiedra
Alberto
A
Fernández
Jesús
J
Gutierrez
Oliver
O
Sánchez
Pedro L
PL
Hernández
Carolina
C
Sanz
Ricardo
R
García-Sancho
Javier
J
Sánchez
Ana
A
D000368:Aged; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D006328:Cardiac Catheterization; D002454:Cell Differentiation; D003080:Cold Temperature / Q000009:adverse effects; D003131:Combined Modality Therapy; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics; D023903:Coronary Restenosis / Q000517:prevention & control; D025401:Echocardiography, Stress; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D015425:Myocardial Reperfusion; D032383:Myocytes, Cardiac / Q000166:cytology; D009924:Organ Culture Techniques; D012038:Regeneration; D033581:Stem Cell Transplantation; D015607:Stents; D013318:Stroke Volume; D000077785:Tenecteplase; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D014182:Transplantation, Autologous; D020257:Ventricular Remodeling / Q000502:physiology*
D018031:Connexin 43; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase