Mesenchymal stem cells (MSCs) are an important choice in regenerative medicine, but their therapeutic potential remains controversial due to challenges in maintaining lineage and vitality. Because MSC injected directly will be eliminated by the host immune system soon, capturing living cells in 3D semi permeable hydrogel matrix can extend the cell retention time, showing great prospects in enhancing the therapeutic effect. However, the effect of hydrogel encapsulation on MSC subgroups is not completely clear. Here, we use the droplet microfluidic technology to manufacture the thin shelled alginate brine gel microcapsule, and control the mechanical properties of the shell by adjusting the molecular weight of alginate. We found that a harder shell than a softer shell can promote the proliferation of mesenchymal stem cells and support their retention in the body. Single cell RNA sequencing confirmed that the hard 3D hydrogel can also promote the maintenance of dryness. Our work demonstrates the potential of hydrogel encapsulated stem cells in long-term therapeutic applications and provides insights into regulating the specific functions of MSC subsets.