Fig. 2

Exosomes mediated microenvironment-based strategies by stem cells. Types of tissue stem cells have been collected from adipose tissue, amniotic fluid, bone marrow, olfactory mucosa, peripheral blood, placenta, umbilical cord blood, and urine. Included stem cells are from multi-differentiation capacity, from well proliferation and differentiation ability, from the potentials of binding biomaterials, from the ease of isolation and culture, or from the non-immunogenicity of autologous transplantation. It has been attempted to summarize an outline for an action of transplantation therapy following the cell treatment against PD [80]. In tissue engineering and regenerative medicine, hUC-MSC that are isolated from human umbilical vein endothelium and subendothelial layer have been broadly approved [81]. Endogenously, MSC exist in connective tissues and interstitium of organs throughout the body. Tissue-derived MSC are one of the important types of adult stem cells, by in vitro conditions, which are shown with self-renewal, proliferation, and multi-differentiation potentials. In the in vitro condition, MSC demonstrate adherent and migrating growth capacity, shown with relatively uniform spindle cells or polygonal cells (hold G0–G1 phase of cell cycle for 80% after 30 passages) presenting normal diploid/maintaining the morphology and proliferation characteristics. MSC highly express CD73, CD90, and CD105 (human gene name: NT5E, THY1, ENG) with adhesion molecule markers such as CD13, CD29, CD44, and CD54 and express low levels of MHC-I molecular markers such as HLA-ABC but show negative for CD34 or CD45, and divergently, for CD31 and other hematopoietic stem cell markers and HLA-DR, HLA-DA, HLA-DP, HLA-DQ, and other MHC-II molecular markers [82]. MSC can express with OCT-4 (human gene name: POU5F1), an embryonic stem cell-characterized marker gene. Specifically, OCT-4/SOX2 in UC-MSC is closely related to maintaining the undifferentiated state of stem cells. Regulation via transcriptional controlling directed multi-lineage differentiation may have included roles in CEBPA gene family members, COL2A1/10A1, DLX5, OPN, OSX (lncRNA MALAT1 pairing), PPARG, RUNX2, SOX9, and Wnt gene family members, of epigenetic mechanisms involving ASH1L, EHMT1/ESET, HDAC1/6/8, KDM4B/6A/6B, or SIRT1/2. Some sorts of exosomes (such as enriched with lncRNA RUNX2-AS1 pairing derived from UC-MSC cell types towards osteogenic differentiation) are particularly useful in the clinical setting as hoped for microenvironment-based targeting of cardiomyocytes, chondrocytes, endothelial cells, germ cells, hepatocytes, neural cells (including glial cells), osteoblasts, skeletal muscle cells, or tumor cells. In addition, application of MSC may possess strong phenotypic plasticity and particularly low immunogenicity