Introduction: Human mesenchymal stem cells (MSCs) are the most popular stem cells applied in disease treatment. MSCs can be isolated and in vitro expanded from various sources such as bone marrow, peripheral blood, umbilical cord blood, umbilical cord tissue, and adipose tissue. According to Dominici et al. (2006), MSCs should express CD105, an essential marker used to confirm MSCs. However, some recent studies have show that MSCs contained a subpopulation that is negative for CD105. This study aimed to compare the immune modulation capacity of 2 populations of CD105 positive (CD105+) and negative (CD105-) MSCs derived from 2 sources: human adipose tissue (AT) and human umbilical cord (UC). Methods: MSCs were isolated from human adipose tissues (adipose tissue-derived mesenchymal stem cells – AT-MSCs) and human umbilical cord (umbilical cord-derived mesenchymal stem cells – UC-MSCs) according to previously published protocols. The two populations of CD105- and CD105+ MSCs were sorted based on the expression of CD105 from AT-MSCs and UC-MSCs. Four populations of CD105 (AT-MSCs, CD105+ AT-MSCs, CD105- UC-MSCs, and CD105+ UC-MSCs) were used to compare the phenotype as well as in vitro differentiation potential; then they were used to evaluate the immune modulation capacity by allogeneic T cell suppression and cytokine release. Results: The results showed that CD105- MSCs from AT and UC exhibited an immune modulation capacity that was much stronger than CD105+ MSCs from the same source of AT and UC. The strong immunomodulation of CD105- MSCs may relate to autocrine production of TGF-beta 1 by MSCs. Conclusion: The results suggested that CD105- MSCs are promising MSCs for application in regenerative medicine, especially for the treatment of diseases related to inflammation.