Intramyocardial Implantation of Bone Marrow-Derived Stem Cells Enhances Perfusion in Chronic Myocardial Infarction: Dependency on Initial Perfusion Depth and Follow-up Assessed by Gated Pinhole SPECT

Intramyocardial Implantation of Bone Marrow–Derived Stem Cells Enhances Perfusion in Chronic Myocardial Infarction: Dependency on Initial Perfusion Depth and Follow-up Assessed by Gated Pinhole SPECT

Nguyen Tran¹^,2, Philippe R. Franken³, Fatiha Maskali²^,4, Joseph Nloga¹, Pablo Maureira¹, Sylvain Poussier⁴, Frederique Groubatch¹, Chris Vanhove³, Jean-Pierre Villemot¹ and Pierre-Yves Marie²^,4

¹ School of Surgery, Faculty of Medicine-UHP, Nancy, France; ² UHP-INSERM U684, Nancy, France; ³ In Vivo Cellular and Molecular Imaging Center, University of Brussels, Brussels, Belgium; and ⁴ Department of Nuclear Medicine, CHU-Nancy, Nancy, France

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FIGURE 1. Evolution of myocardial perfusion, as assessed by sestamibi uptake, in the analyzed segments overall (A), in MI segments only (B), and in MI segments from treated rats only (C). (A) Segments were classified as belonging (circles) or not belonging (squares) to underperfused areas ( $≤$ 70% uptake on pretherapeutic SPECT) and were compared between treated rats (n = 118 [ ${square}$ ] and 32 [ ${circ}$ ]) and untreated rats (n = 95 [ ${blacksquare}$ ] and 25 [•]). (B) Segments were classified as having (triangles) or not having (diamonds) severe perfusion defects (<60% uptake) before transplantation and were compared between treated rats (n = 19 [ ${diamond}$ ] and 13 [ ${triangleup}$ ]) and untreated rats (n = 13 [ ${diamondsuit}$ ] and 12 [ ${blacktriangleup}$ ]). (C) Segments were classified as having (triangles) or not having (diamonds) severe perfusion defects (<60% uptake) before transplantation and were compared between rats that had (n = 10 [ ${diamondsuit}$ ] and 4 [ ${blacktriangleup}$ ]) and rats that did not have (n = 8 [ ${diamond}$ ] and 10 [ ${triangleup}$ ]) early retention of ¹¹¹In-BMSCs. *P < 0.05 for unpaired comparisons. TT= treated; UT = untreated.

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FIGURE 2. ^99mTc-Sestamibi pinhole SPECT images of untreated rat 1, 3, 5, and 7 mo after MI. Perfusion defects clearly worsened over time. A = anterior wall; I = inferior wall; L = lateral wall; and S = septal wall.

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FIGURE 3. ^99mTc-Sestamibi pinhole SPECT images of treated rat 1, 3, 5, and 7 mo after MI and, in center column, dual ¹¹¹In/^99mTc-sestamibi pinhole SPECT images 48 h after transplantation. Perfusion improved in areas that had only moderate defects before treatment (around 60% uptake), both at implantation site (black arrow) and at neighboring site (white arrow). A = anterior wall; I = inferior wall; L = lateral wall; and S = septal wall.

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FIGURE 4. ^99mTc-Sestamibi pinhole SPECT images of treated rat 1, 3, 5, and 7 mo after MI and, in center column, dual ¹¹¹In/^99mTc-sestamibi pinhole SPECT images 48 h after transplantation. No clear improvement in perfusion was seen in area that had severe defects before treatment (<50% uptake; black arrow) and where the greatest number of implanted cells had been detected. By contrast, improvement of perfusion was clear in neighboring area that had less severe defects before treatment (white arrows). A = anterior wall; I = inferior wall; L = lateral wall; and S = septal wall.

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FIGURE 5. ^99mTc-Sestamibi pinhole SPECT images of treated rat 1, 3, 5, and 7 mo after MI and, in center column, dual ¹¹¹In/^99mTc-sestamibi pinhole SPECT images 48 h after transplantation. BMSCs were injected in core of MI area with severe perfusion defects (<50% of sestamibi uptake), and no clear improvement in perfusion was seen after transplantation. A = anterior wall; I = inferior wall; L = lateral wall; and S = septal wall.