Post-traumatic heterotopic ossification in front of the ankle joint for 23 years:A case report and review of literature

BACKGROUND Heterotopic ossification(HO)refers to the formation of new bone in non-skeletal tissues such as muscles,tendons or other soft tissues.Severe muscle and soft tissue injury often lead to the formation of HO.However,anterior HO of the ankle is rarely reported.CASE SUMMARY We report a patient with massive HO in front of the ankle joint for 23 years.In 1998,the patient was injured by a falling object on the right lower extremity,which gradually formed a massive heterotopic bone change in the right calf and dorsum of the foot.The patient did not develop gradual ankle function limitations until nearly 36 mo ago,and underwent resection of HO.Even after 23 years and resection of HO,the ankle joint was still able to move.CONCLUSION It is recommended that the orthopedist should be aware of HO and distinguish it from bone tumor.

Generation of tetraploid complementation mice from embryonic stem cells cultured with chemical defined medium

Mouse embryonic stem cells(mESCs)derived from inner cell mass(ICM)of pre-implantation embryos,can maintain undifferentiated state when cultured in N2B27 medium supplemented with GSK3inhibitor CHIR99021 and MEK inhibitor PD0325901(‘‘2i’’)and leukemia inhibitor factor(LIF).Compare to conventional culture medium,all components of this medium are defined.With the N2B27 medium,‘‘2i’’and LIF,mESCs can contribute to the germline of the chimeric embryos,however,whether the‘‘all-ES cells’’mice can been generated by tetraploid complementation is unclear yet,while the tetraploid complementation serve as a golden standard to assess the pluripotency of ES cells.Here,our study showed that mESCs derived and cultured with the N2B27 complete medium could generate fertile mice by tetraploid complementation.In addition,the survival rate of tetraploid complementation mice produced by inbred mES cell lines is higher than the conventional culture condition,and increased the percentage of Oct4 positive cells contrast to conventional medium either.Therefore,the N2B27 medium supplemented with‘‘2i’’and LIF is an alternative choice forthe derivation and long-term culture of mouse embryonic stem cells.

Pluripotency of Induced Pluripotent Stem Cells

Induced pluripotent stem （iPS） cells can be generated by forced expression of four pluripotency factors in somatic cells. This has received much attention in recent years since it may offer us a promising donor cell source for cell transplantation therapy. There has been great progress in iPS cell research in the past few years. However, several issues need to be further addressed in the near future before the clinical application of iPS cells, like the immunogenieity of iPS cells, the variability of differentiation potential and most importantly tumor formation of the iPS derivative cells. Here, we review recent progress in research into the pluripotency of iPS cells.

Specification of functional neurons and glia from human pluripotent stem cells

Human pluripotent stem cells(PSCs)such as embryonic stem cells(ESCs)and induced pluripotent stem cells(iPSCs)hold great promise in regenerative medicine as they are an important source of functional cells for potential cell replacement.These human PSCs,similar to their counterparts of mouse,have the full potential to give rise to any type of cells in the body.However,for the promise to be fulfilled,it is necessary to convert these PSCs into functional specialized cells.Using the developmental principles of neural lineage specification,human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia,such as striatal gama-aminobutyric acid(GABA)-ergic neurons,spinal motor neurons and myelin sheath forming oligodendrocytes.The human PSCs,in general differentiate after the similar developmental program as that of the mouse:they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate transition.However,the human PSCs,unlike their counterparts of mouse,tend to respond divergently to the same set of extracellular signals at certain stages of differentiation,which will be a critical consideration to translate the animal model based studies to clinical application.

Induced Pluripotency for Translational Research

The advent of induced pluripotent stem cells （iPSCs） has revolutionized the concept of cellular reprogramming and potentially will solve the immunological compatibility issues that have so far hindered the application of human pluripotent stem cells in regenerative medicine. Recent findings showed that pluripotency is defined by a state of balanced lineage potency, which can be artificially instated through various procedures, including the conventional Yamanaka strategy. As a type of pluripotent stem cell, iPSCs are subject to the usual concerns over purity of differen- tiated derivatives and risks of tumor formation when used for cell-based therapy, though they pro- vide certain advantages in translational research, especially in the areas of personalized medicine, disease modeling and drug screening, iPSC-based technology, human embryonic stem cells （hESCs） and direct lineage conversion each will play distinct roles in specific aspects of translational medi- cine, and continue yielding surprises for scientists and the public.