Artificial cell microencapsulated stem cells in regenerative medicine, tissue engineering and cell therapy

Abstract

Adult stem cells, especially isolated from bone marrow, have been extensively investigated in recent years. Studies focus on their multiple plasticity oftransdifferentiating into various cell lineages and on their potential in cellular therapy in regenerative medicine. In many cases, there is the need for tissue engineering manipulation. Among the different approaches of stem cells tissue engineering, microencapsulation can immobilize stem cells to provide a favorable microenvironment for stem cells survival and functioning. Furthermore, microencapsulated stem cells are immunoisolated after transplantation. We show that one intraperitoneal injection of microencapsulated bone marrow stem cells can prolong the survival of liver failure rat models with 90% of the liver removed surgically. In addition to transdifferentiation, bone marrow stem cells can act as feeder cells. For example, when coencapsulated with hepatocytes, stem cells can increase the viability and function of the hepatocytes in vitro and in vivo.

Figure 1

The schematic protocol of the use of bone marrow stem cells to enhance hepatocytes viability and specific function. The bone marrow stem cells and hepatocytes were coencapsulated, this enhanced the hepatocytes viability both in culture and in transplantation into rats. This coencapsulation also enhanced hepatocytes’ specific function of ammonium conversion in culture and of lowering blood bilirubin after implantation into hyperbilirubinemia Gunn rats.

Figure 2

Histology and survival study of microencapsulated bone marrow stem cells transplantation into 90% hepatectomized rat model. A) microcapsules with bone marrow cells before transplantation. Original magnification × 40. B) HE staining of microcapsules recovered 2 weeks post transplantation. Original magnification × 400. C) PAS cytochemical glycogen stain for the recovered microencapsulated bone marrow stem cells. Positive cells showed pink staining in cytoplasm. Original magnification × 1000. D to G) Immunocytochemistry staining of the recovered microencapsulated bone marrow 2 week post transplantation, for albumin D), cytokeratin 8 E), cytokeratin 18 F), alpha-fetoprotein G). Dark brown cells indicate the positive cells. Original magnification × 1000. H)Kaplan-meier survival curve, at week 2 post transplantation, rats transplanted with microencapsulated bone marrow stem cells (encap BM) survived longer than the partial hepatectomy(PH) group, empty microcapsules(emp cap) group and the free bone marrow cells(free BM) group, comparable to the sham operation(sham OP) group, n = 6 in each group. (Reprinted with permission from John Wiley and Sons, Inc. Liu ZC, Chang TM. Transdifferentiation of bioencapsulated bone marrow cells into hepatocyte-like cells in the 90% hepatectomized rat model. Liver Transpl 2006; 12:566–572.)

Figure 3

Mechanism of therapeutic effect of encapsulated bone marrow stem cells transplantaed into 90% hepatectomized rats. The encapsulated bone marrow cells are immunoisolated from imunorejection by antibodies and inflammatory cells, whereas the nutrients and oxygen can pass freely through the capsular membrane, growth factors and cytokines secreted by the stem cells can diffuse out the microcapsules into peritoneal cavity, then were drained into portal venous system into the liver to enhance the liver regeneration.