Xenotransplantation Reveals Regenerative Potential of Expanded HuSCs
(A) Four weeks after transplantation, engraftment of freshly isolated quiescent huSCs, control activated huSCs, and p38i-treated activated huSCs was determined by IF analysis of human-specific ITGB1 expression (magenta); 3 × 104 cells were used for each transplant. Anti-laminin (green) detects laminin of mouse and human origin.
(B) Representative low-magnification (left) and high-magnification (right) images of engrafted p38i-treated activated huSCs 4 weeks after transplantation into mouse muscle. The yellow arrowhead identifies a sublaminar PAX7-expressing cell of human origin; the yellow arrow identifies a nearby sublaminar Pax7-expressing cell of mouse origin.
(C) Representative flow cytometric analysis of human-specific ITGB1 expression in the bulk population of mononuclear cells isolated from mouse muscle transplanted with 3 × 104 huSCs per transplant. Quantification of total mononuclear human ITGB1-expressing cells per transplanted muscle revealed a 3.6-fold and 7.7-fold increase in engraftment of p38i-treated huSCs relative to quiescent huSCs and untreated activated huSCs, respectively. ∗∗∗p < 0.001 comparing p38i-treated activated huSCs to control activated huSCs or quiescent huSCs (n = 4 per condition). Error bars represent SD.