It has been widely reported that cell size and morphology affects the therapeutic effect of MSC.56-59 These previous studies showed the features of small size MSC that are high expression of NANOG, POU5F1 and IDO1, and lower expression of α-SMA.58,59 Further, small size MSC exhibit higher therapeutic effect on elastase-induced emphysema model and myosin-induced experimental autoimmune myositis by inhibiting chronic inflammation.46,58 These results indicated that multi factors including GDNF improved by 3D-BMSC, which enhanced the therapeutic effect of BMSC to MRL/lpr mice. The gene discussed is POU5F1; the disease is pulmonary emphysema.