Bone marrow-derived B cells preserve ventricular function after acute myocardial infarction.
OBJECTIVE
In view of evidence that mature cells play a role in modulating the stem cell niche and thereby stem cell potential and proliferation, we hypothesized that a mature bone marrow (BM) mononuclear cell (MNC) infusion subfraction may have particular potency in promoting hematopoietic or resident stem cell-induced cardiac repair post-infarction.


BACKGROUND
Treatment of acute myocardial infarction (MI) with BM MNC infusion has shown promise for improving patient outcomes. However, clinical data are conflicting, and demonstrate modest improvements. BM MNCs consist of different subpopulations including stem cells, progenitors, and differentiated leukocytes.


METHODS
Stem cells (c-kit+) and subsets of mature cells including myeloid lineage, B and T-cells were isolated from bone marrow harvested from isogeneic donor rats. Recipient rats had baseline echocardiography then coronary artery ligation; 1 x 10(6) cells (enriched subpopulations or combinations of subpopulations of BM MNC) or saline was injected into ischemic and ischemic border zones. Cell subpopulations were either injected fresh or after overnight culture. After 2 weeks, animals underwent follow-up echocardiography. Cardiac tissue was assayed for cardiomyocyte proliferation and apoptosis.


RESULTS
Fractional ventricular diameter shortening was significantly improved compared with saline (38 +/- 3.2%) when B cells alone were injected fresh (44 +/- 3.0%, p = 0.035), or after overnight culture (51 +/- 2.9%, p < 0.001), or after culture with c-kit+ cells (44 +/- 2.4%, p = 0.062). B cells reduced apoptosis at 48 h after injection compared with control cells (5.7 +/- 1.2% vs. 12.6 +/- 2.0%, p = 0.005).


CONCLUSIONS
Intramyocardial injection of B cells into early post-ischemic myocardium preserved cardiac function by cardiomyocyte salvage. Other BM MNC subtypes were either ineffective or suppressed cardioprotection conferred by an enriched B cell population.
AC Therapeutics, Inc., Norcross, Georgia, USA.
Traci T
TT
Goodchild
Keith A
KA
Robinson
Wenxin
W
Pang
Fernando
F
Tondato
Jianhua
J
Cui
Johnail
J
Arrington
Lisa
L
Godwin
Mark
M
Ungs
Nadia
N
Carlesso
Nadine
N
Weich
Mark C
MC
Poznansky
Nicolas A F
NA
Chronos
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000737:chemistry / Q000637:transplantation*; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left
D019009:Proto-Oncogene Proteins c-kit