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뇌졸중 치료에서 성체 간엽 줄기세포 치료의 현재와 미래
김영인 ( Yeong In Kim ),오일환 ( Il Hoan Oh ) 한국조직공학과 재생의학회 2005 조직공학과 재생의학 Vol.2 No.3
Mesenchymal stem cells (MSC) can be isolated from several tissues such as bone marrow, umbilical cord and adipose tissue, but easily accessible bone marrow seems to be the most common source. These adult stem cells may not be as ``powerful`` or diverse as embryonic stem cells may one day become, but at present they offer many advantages for developing cellular therapeutics: ease of isolation, expansion potential, stable phenotype, shippability, and compatibility with different delivery methods and formulations. Their potential use as cellular therapeutics has prompted the investigation of interactions of allogeneic MSC with the immune response. It remains uncertain which type of cell would be most appropriate for cell therapy in stroke. The ethical dilemmas of embryonic stem cell research and the problems associated with allotransplantation and xenotransplantation limit the clinical use of stem cells. Recent experimental studies raised the possibility of using MSCs as stroke therapy. We have reviewed some of the recent developments of MSC in the treatment of stroke.
무혈청 배지와 우태아 혈청의 인간조혈모세포에 대한 유전자 전달에 미치는 효과 비교분석
문누리 ( Noo Ry Moon ),강영주 ( Young Ju Kang ),박보배 ( Bo Bae Park ),오일환 ( Il Hoan Oh ) 한국조직공학·재생의학회 2007 조직공학과 재생의학 Vol.4 No.1
High efficiency gene transfer into hematopoietic stem cells(HSCs) is essential for application of HSCs for gene therapeutic trials as well as manipulation of the HSCs. Here we examined the influence of fetal bovine serum(FBS) in the medium during retroviral gene transduction of marker gene(GFP; green fluorescent protein) into human CD34+cells in comparison to serum substitution medium(SFM). First, during the ex vivo culture of CD34+ cells for 5 days, comparable level of expansion in total CD34+ cells and colony forming cells were observed between FBS containing medium and SFM. Similarly, total engraftement level achieved after xenotransplantation of cultured cells into Non-diabetic severe combined immune deficiency(NOD/SCID) were comparable for both medium conditions. In contrast the virus protecting effect was significantly higher for FBS containing medium as determined by number of infective particles dervied from producer cells. When retroviral gene transfer into purified CD34+ cells were compared, overall gene transfer efficiency was higher for FBS contaiing medium(50±8.1%) than SFM(25±6.0%)(p=0.009). Similarly gene transfer efficency into colony forming cells and CD34+ cells were significantly higher for FBS group as compared to SFM group. Taken together, these results show that while SFM can preserve CD34+ to a comparable level, FBS medium can protect viral particle to cause a more efficent gene transfer into hematopoietic progenitor cells.
김진아 ( Jin A Kim ),윤건호 ( Kun Ho Yoon ),안지연 ( Ji Yeon Ahn ),오일환 ( Il Hoan Oh ) 한국조직공학과 재생의학회 2006 조직공학과 재생의학 Vol.3 No.2
Hepatocyte growth factor (HGF) is a pleiotriphic growth factor with diverse cellular function including morphogenesis, cell migration, and growth controls. In addition to their major physiologial function for growth and differentiation of hepatocyte, it has been implicated in the regulation of hematopoietic system. While graft vs. host disease could be supprressed with HGF, stimulatory effect on blood cell production was also observed during in vitro long-term culture. In the present study, we have examined the susceptibility of each hematopoietic component to HGF signal through expression of their receptor c-met. We show that the contrasting effect of HGF could be caused from compartmental expression of c-met between stromal cells and hematopoietic cells. Thus c-met-HDF signaling axis could be a mediator for cellular interaction between hematopoietic and their microenvironment.
조혈전구세포의 시험관 증식 및 분화에 대한 HoxB4와 STAT3의 상호조절 연구
홍성현 ( Sung Hyun Hong ),양승집 ( Seung Jip Yang ),김진아 ( Jin A Kim ),오일환 ( Il Hoan Oh ) 한국조직공학·재생의학회 2007 조직공학과 재생의학 Vol.4 No.2
Self-renewal of hematopoietic stem cells(HSC) is a major mechanism for regeneration of blood tissues from HSCs. Previous studies have identified HoxB4 and STAT3 as an important molecular mechanisms regulating HSC self-renewal, but potential interaction of the two remains unknown. To address the issue, transgenic mice for constitutively activated STAT3(STAT3-C) was examined for HoxB4 expression, but no difference in the HoxB4 expression level was seen compared to the control mice. On the contrary, when HoxB4 was co-transduced with dominant negative(dnSTAT3), the enhancing effect of HoxB4 on the proliferation of 5-FU stimulated bone marrow cells were significantly decreased as compared to the HoxB4 alone group. Similarly, the effect of HoxB4 on the maintenance of undifferentiated state as determined by lineage marker was significantly deteriorated by co-expression of dnSTAT3. Taken together, these results suggest that STAT3 activity could be a down-stream of HoxB4, being required for HoxB4-mediated enhancing effects on in vitro cultured hematopoietic precursor cells.
NOD/SCID 마우스 모델을 이용한 인간 제대혈 혼합이식에서의 생착 양상 분석
정양조,김동욱,조빈,강영주,박보배,김혜정,김태규,오일환 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.2
연구배경: 제대혈은 골수에 비해 많은 장점을 가지고 있음에도, 이식 후 성적에 있어 총세포수에 의해 좌우되며, 한 개의 태반으로부터 얻을 수 있는 총세포수의 한계가 있어 주로 소아에 국한되고 있다. 따라서 제대혈 응용의 확대를 위해 생착량을 늘이기 위한 방법으로 다중공여자에 의한 제대혈 혼합이식을 늘일 수 있는지 연구하기 위하여, 본 연구에서는 주조직적합성 형별로 조합된 제대혈을 NOD/ SCID 생쥐에 이식하는 방법으로, 혼합생착의 가능성을 연구하였다. 방법: 조합된 2개 공여자로부터 얻어진 제대혈들을 단일이식 및 혼합이식하여, 혼합이식된 숙주에 생착된 세포를 PCR-SSOP 방법을 사용하여 공여자 별로 추적하였다. 또한 각 공여자세포의 상대적 생착비율을 대조군인 단일제대혈 이식에서 얻어진 생착량과 비교하는 정량적 비교도 함께 하였다. 결과: 총단핵구를 혼합이식한 실험군에서는 주조직적합성의 일치도에 관계없이 한쪽공여자의 세포가 다른쪽에 비해 우세한 편향생착을 보였다. 그러나 임파구를 비롯한 Lineage 양성세포를 제거한 실험군에서는 주조직적합성의 불일치에도 불구하고 뚜렸한 생착의 공존이 관찰되었다. 결론: 본 연구는 제대혈의 생착량을 증가를 목적으로 총단핵구를 혼합이식할 경우 한쪽공여자의 세포에 의해 편중되며, 이것을 이식 후 생착과정에서의 두 종류의 세포의 경쟁에 의해 초래된다는 것을 보이고 있다. 또한 이러한 경쟁은 제대혈에 포함되어 있던 임파구들에 의한 것이며, 생착공존을 위하여는 공여자간 주조직적합성의 일치도 보다, 임파구의 제거가 더 중요하다는 것을 보여주고 있다. Background: Although umbilical cord blood (UCB) has been an attractive alternatives for bone marrow cells, application is limited to pediatric case due to limitation in total number of nucleated cells, that is a single most important factor for outcomes of UCB transplantation. Therefore, increasing overall engraftment by mixed transplantation of UCB derived from multiple donor should comprise one strategy to circumvent the posed limitation of UCB transplantation. In order to investigate the feasibility of establishing co-engraftment by multi-donor UCB cells, we carried out a xenotransaplantation study using NOD/SCID mice for systemic analysis of results on the input-based control of single unit transplantation. Methods: UCB units with various extent of HLA-matchings were co-transplanted into NOD/SCID mice along with single unit transplantation control. The relative contributions of engraftment by cells from each donor-derived were analyzed by HLA polymorphism using PCR-SSOP. Results: In all HLA-based mixed transplantation of total nucleated UCB cells, engraftment of one donor predominated over the other despite that equivalent amount of engraftments were achieved by single donor transplantation. When lineage depleted UCB units were co-transplanted, significant degree of co-engraftments were observed regardless of HLA disparity. Conclusion: Our result show that one donor cells dominate over the other in mixed UCB transplantation and that it is due to competition between donor cells during post-transplantation process. Our results suggest that immune cells contained in UCB unit mediate such competitioin and that 6 locus HLA matching would not be sufficient to prevent the competition.