Wharton’s Jelly or Bone Marrow Mesenchymal Stromal Cells Improve Cardiac Function Following Myocardial Infarction for More Than 32 Weeks in a Rat Model: A Preliminary Report
Yelica López, Barbara Lutjemeier, Kiran Seshareddy, Elizabeth M. Trevino, K. Sue Hageman, Timothy I. Musch, Michele Borgarelli and Mark L. Weiss
Affiliation: Department of Anatomy and Physiology, Kansas State University, Coles Hall, room 105, Manhattan, KS 66506, USA
Keywords: Bone marrow, cardiomyocyte differentiation, cellular therapy, mesenchymal stromal cells, myocardial ischemia,
preclinical testing, rat, echocardiography, regenerative medicine, umbilical cord, Wharton’s jelly.
The therapeutic effect of mesenchymal stromal cells (MSCs) following myocardial infarction (MI) is small.
This may be due to differences in cellular sources and donor age, route of administration, in vitro cellular manipulations
and the short time course of follow up in many animal studies. Here, we compared MSCs from two different sources
(adult bone marrow or Wharton’s jelly from umbilical cord) for their long-term therapeutic effect following MI in a rat
model to evaluate the effect of donor age. MSCs (or control infusions) were given intravenously 24-48 hr after myocardial
ischemia (MI) induced by coronary artery ligation. Cardiac function was assessed by ultrasound at time points starting
from before MSC infusion through 68 weeks after MI. A significant improvement in ejection fraction was seen in animals
that received MSCs in time points 25 to 31 wks after treatment (p <0.01). These results support previous work that show
that MSCs can cause improvement in cardiac function and extend that work by showing that the beneficial effects are durable.
To investigate MSCs’ cardiac differentiation potential, Wharton’s jelly MSCs were co-cultured with fetal or adult
bone-derived marrow MSCs. When Wharton’s jelly MSCs were co-cultured with fetal MSCs, and not with adult MSCs,
myotube structures were observed in two-three days and spontaneous contractions (beating) cells were observed in fiveseven
days. The beating structures formed a functional syncytium indicated by coordinated contractions (beating) of independent
nodes. Taken together, these results suggest that MSCs given 24-48 hr after MI have a significant and durable
beneficial effect more than 25 weeks after MI and that MSC treatment can home to damaged tissue and improve heart
function after intravenous infusion 24-48 hrs after MI, and that WJCs may be a useful source for off-the-shelf cellular
therapy for MI.
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