干细胞治疗在心脏手术中的应用

shenxiu2

之前麻醉了一个49岁的男病人做心血管绕道手术.同时也做干细胞治疗.他在一个月前已被抽取骨髓去培植,现在已被处理过的干细胞就被专员从实验室用装着液体氮的容器带来了手术室.外科同事把干细胞suspend 在0.9% NaCl 里,然后注射到心肌坏死部分的周边.这病人的心脏衰竭.(Ejection fraction =20%.),很大部份心肌都已坏死.因此决定做这治疗.虽然花费很高,也愿意尝试.

   这是本院第五宗病例.根据复诊 Echocardiogram 记录,病人的心肌功能改善,从前坏死的部分已能见到收缩功能.看来是有前景的一种治疗.

   据报道,干细胞治疗目前只在心脏治疗和软骨治疗方面有可见疗效,其他如脊髓神经和肾脏治疗,都还在研究中.

a0a0a0b0

照此说，脐带血采集还是有意义的。

shenxiu2

根据研究人员说,脐带血并不适合于这种治疗.
脐带血多用于治疗血癌之类的疾病,如骨髓移植.是因所含干细胞的数量和种类不同.它们还需要经过处理和分类,才去培养.

xyz-cn99

　　楼主可否详细介绍下相关手术过程和围术期管理的经验？感谢您的分享。华西也有老师正在做这一方面的研究，不过还仅在实验室开展。

shenxiu2

手术过程和围术期管理都和一般的心血管绕道手术一样,只是或许由于做此治疗的病人都是严重心衰竭,很差的ejection fraction,所以在 off bypass 时需要多些药物的支持。
治疗关键是干细胞的采集和处理。培植了的这些约二千万到二万万干细胞已被suspend在10 ml 或20 ml 的 0。9%NaCl  里。外科医生在做完所有绕道血管的缝合后，在还没有off bypass 之前把这些干细胞注射在epicardium,scar tissue周边。手术过程非常简单。
在我国这是先驱的尝试。
我院心肺外科医生联同作干细胞研究的医师合撰了一份研究报导，我能拿到就转来论坛。

shenxiu2

转自http://www.cytopeutics.com/Stem_Cell.html

Stem Cells
What are Stem Cells?

Stem cells are cells that have the ability to self-replicate and differentiate into specialized cells such as heart, brain, nerve, liver, skin, and bone and therefore potentially have the ability to treat diseases and injuries involving these organs. Stem cells must not be confused with progenitor or precursor cells; whereas stem cells have the ability to transform into multiple cells types, progenitor cells are committed to a certain linage. For example, a hematopoietic cell is destined to become only blood cells.
True pluripotent stem cells only exist in the first 14 days of life of embryo. WE DO NOT USE FETAL OR EMBRYONIC STEM CELL. The usage of embryonic stem cells has unresolved ethical concerns, known to be tumorigenic and is not permitted in Malaysia. At Cytopeutics, we are harvesting only adult stem cells. Among our core adult stem cell types is the Mesenchymal Stem Cells, which is multipotent and has the ability to transform into multiple cell types.

What is Mesenchymal Stem Cell ?
Mesenchymal Stem Cell (MSC) is true adult multipotent stem cell that has been shown differentiate or trans-differentiate into fat, cartilage, bone, skeletal muscle, cardiac muscle, neurons, mesangial cells, epithelial cells and liver cells. MSC can be found mainly in bone marrow which is widely acknowledged as the purer, richer and safer source of MSC. Other adult sources of MSC are umbilical cord blood, peripheral blood and fat. Researchers found that MSC are very rare in peripheral blood and umbilical cord blood and cannot be consistently obtained. Some used growth factors to stimulate “stem cells” into blood circulation, however mainly hematopoietic progenitor cells but not MSC that were being stimulated. This process has also led to high rates of coronary stent restenosis (blockage of the coronary stent) in some heart patients.


MSC Collection Method

MSC is purest and most abundant in bone marrow MSC make up 1:1000 BMMNC population
Bone marrow is currently known to be the purer, richer and safer source of MSC; therefore in order to get the MSC as pure and unadulterated as possible it is best to harvest from the bone marrow, which is regarded as the “stem cell niche”. MSC are collected from patient’s own bone marrow via Bone Marrow Aspiration (BMA) by a qualified physician. BMA is a common procedure undertaken by hematologists or qualified physicians in which a small amount of bone marrow is aspirated from patient’s pelvic bone, normally the iliac crest. It is a simple, convenient, safe and quick procedure where the whole process usually requires less than 20 minutes and it can be done under local anesthesia. Collected bone marrow cells are then sent to our Clean Room 100 laboratory to be processed by our highly qualified scientist with utmost professionalism and care.

MSC Research
Research on MSC is expanding exponentially.  Researchers around the world, including Cytopeutics have proven that MSC not only can differentiate into tissues of mesodermal origin such adipocytes, chondrocytes, osteocytes, cardiomyocytes, but also can trans-differentiate into tissues of ectodermal origin such as neurons and epithelial cells, and endodermal origin such as insulin-producing islet cells and hepatocytes in vitro and in vivo.
In addition, Cytopeutics is one of the few groups that have successfully induced MSC into mesangial cells and nerve cells apart from heart cells, cartilage cells and skin tissues. We are also actively researching into stem cell treatment for kidney disease, diabetes, cancer and exploring the possibility of allogenic MSC treatment (stem cells transplantation from one donor to another individual).

MSC Clinical Trials and Potential Therapies
Since MSC are multipotent stem cells that can differentiate into many cell types, the potential clinical indications for MSC becoming endless.  MSC have been explored in treating heart failure, myocardial infarction (heart attack), osteoarthritis, stroke and spinal cord injury around the world and the results are promising. In addition, the results of thousands of patients whom have received MSC so far had shown MSC are safe and feasible to be transplanted into patients without any short- or long-term side effects up to 10 years.
MSC is also immunopriviledged and immunosuppressive with strong anti-inflammatory properties that allow it to be tested against autoimmune diseases such as Graft Versus Host Disease (GVHD), Crohn’s disease, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
In Malaysia, we currently have concluded our research in heart failures, heart attack, refractory angina, osteoarthritis, peripheral artery disease and foot ulcer, and we will progressively offer clinically-tested pilot programmes under observation with utmost professionalism.

Heart Failure, Heart Attack and Dilated Cardiomyopathy
1.        Abdel-Latif et al., Adult bone marrow-derived cell for Cardiac repair. American Medical Association 2007
2.        Chen et al, Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. The American Journal of Cardiology 2004
3.        G. Katritsis et al, Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium. Catheterization and Cardiovascular Interventions 2005
4.        Mandana et al, Autologous In vitro expanded mesenchymal stem cell therapy for human old myocardial infarction. Archieves of Iranian Medicine 2007
5.        Minguell and Erices, Mesenchymal stem cells and the treatment of cardiac disease. Experimental Biology and Medicine 2006
6.        Pittenger and Martin, Mesenchymal stem cells and their potential as cardiac therapeutics. Circulation Research 2004
7.        Choong et al., Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro. Cytotherapy 2007
8.        Toma et al., Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002
9.        Assmus et al., Transcoronary Transplantation of progenitor cells after myocardial infarction. The New England Journal of medicine 2006
10.        Wong et al., Differentiation of human mesenchymal stem cells into mesangial cells in post-glomerular injury murine model. Pathology 2008
11.        Zohlnhofer et al., Stem cell mobilizatiopn by granulocyte colony-stimulation factor for myocardial recovery after acute myocardial infarction. Journal of the American College of Cardiology 2008
12.        Chen et al., Intracoronary Transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left enterior descending artery. The Journal of Invasive Cardiology 2006
13.        Widimsky et al., Intracoronary transplantation of bone marrow stem cells: background, technique, and limitations. European Heart Journal Supplements 2006
14.        Yeerebakan et al., Safety of intramyocardial stem cell therapy for the ishemic myocardium: Result of the rostock trial after 5-year follow-up. Cell Transplantation 2007
15.        Martino et al., Cell therapy in dilated cardiomyopathy. Arquivos Brasileiros de Cardiologia 2006
16.        Vilas-Boas et al., Early result of bone marrow cell transplantation to the myocardium of patients with heart failure due to Chagas disease. Arquivos Brasileiros de Cardiologia 2006
17.        Schachinger et al., Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. The New England Journal of Medicine 2006
18.        Lunde et al., Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. he New England Journal of MedicineT 2006
19.        Practical Handbook of advanced interventional cardiology.

Osteoarthritis and Other Cartilage Defects
1.        Lee et al., Injectable mesenchymal stem cell therapy for large cartilage defects-a porcine model. Stem Cells 2007
2.        Yang et al., Cartilage Regeneration by Delayed Engraftment of an injectable fibrin clue/hyaluronate hybrid scaffold mixed with mesenchymal stem cells. Journal of US-China Medical Science 2007
3.        Im et al., Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow. Journal Bone Joint Surgery 2001
4.        Danisovic et al., Chondrogenic differentaition of human bone marrow and adipose tissue-derived mesenchymal stem cells. Journal of  Applied Biomedicine 2007
5.        Tuan, Stemming cartilage degeneration: Adult mesenchymal stem cells as a cell source for a articular cartilage tissue engineering. Arthritis & Rheumatism 2006
6.        Tuan et al., Review adult mesenchymal stem cells and cell-based tissue engineering. Arthritis research and Therapy 2002
7.        Fibbe, Mesnchymal stem cells. A potential source for skeletal repair. Ann Rheum Dis 2002
8.        Choong et al., Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro. Cytotherapy 2007
9.        Fei Chang et al., repair of large full-thickness articular cartilage defects by transplantation of autologous uncultured bone-marrow-derived mononuclear cells. Journal of Orthopaedic research 2008
10.        Wakitani et al., Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. Journal of Tissue Engineering and Degenerative medicine 2007
11.        Kuroda et al., Brief report-Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis and Cartilage2007
12.        Wakitani et al., Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritis knees. Osteoarthritis and Cartilage 2007
13.        Centeno et al., Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, Autologous mesenchymal stem cells. Pain Physician Journal 2008
14.        Centeno et al., regeneration of meniscus cartilage in a knee treated with percutaneously implanted autolpgous mesenchymal stem cells. Medical Hypotheses 2008
15.        Wong et al., Differentiation of human mesenchymal stem cells into mesangial cells in post-glomerular injury murine model. Pathology 2008

Degenerative Intervetebral Disc Disease
1.        Richardson et al., Intervertebral Disc Cell–Mediated Mesenchymal Stem Cell Differentiation. Stem Cells 2005
2.        Acosta et al., The potential role of mesenchymal stem cell therapy for intervertebral disc degeneration: a critical overview. Neurosurg Focus 2005
3.        Steck et al., Induction of intervertebral disc–like cells from adult mesenchymal stem cells. Stem cells 2005
4.        Mwale et al., Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: A requisite for tissue engineering of intervertebral disc. Europen Cells and Materials 2004
5.        Hughes et al., Differentiation of mesenchymal stem cells (MSCs) to NP-like cells in Chitosan/Glycerol Phosphate: Implications for tissue engineering of the intervertebral disc(IVD). Europen Cells and Materials 2005
6.        Cheung et al., Regeneration of nucleus pulposus after discectomy by autologous mesenchymal stem cells: a rabbit model.Europen Cells and Materials 2005
7.        Richardson et al., Differentiation of human mesenchymal stem cells to nucleus pulposus cells using a novel co-culture technique.Europen Cells and Materials 2005
8.        Leung et al., Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. European Spine Journal 2006
9.        Bagaria et al., Stem cells in orthopeadic: current concepts and possible future applications. Indian Journal Medicine Science 2006
10.        Choong et al., Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro. Cytotherapy 2007
11.        Wong et al., Differentiation of human mesenchymal stem cells into mesangial cells in post-glomerular injury murine model. Pathology 2008

Stroke
1.        Choong et al., Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro. Cytotherapy 2007
2.        Bang et al, Autologous Mesenchymal Stem Cell Transplantation in Stroke Patients. American Neurological Association 2005
3.        Chen et al., Intravenous Bone Marrow Stromal Cell Therapy Reduces Apoptosis and Promotes Endogenous Cell Proliferation After Stroke in Female Rat. Journal of Neuroscience Research2003
4.        Chen et al., Intravenous Administration of Human Bone Marrow Stromal Cells Induces Angiogenesis in the Ischemic Boundary Zone After Stroke in Rats. Circulation Research 2003
5.        Shen et al., Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke. Journal of Cerebral Blood Flow & Metabolism 2007
6.        Shen at al., One-Year Follow-Up After Bone Marrow Stromal Cell Treatment in Middle-Aged Female Rats With Strok. Stroke 2007
7.        Kopen at al., Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Cell Biology 1999
8.        Guzman et al., Intravascular cell replacement therapy for stroke. Neurosurg Focus 2008
9.        Shen et al., Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 2008
10.        Chen et al., Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. Neurological Science 2001
11.        Hermann et al., Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells. Journal of Cell Science 2004
12.        Kyung et al., Neurons Derived From Human Mesenchymal Stem Cells Show Synaptic Transmission and Can Be Induced to Produce the Neurotransmitter Substance P by Interleukin-1α. Stem Cells 2005
13.        Zacharek et al., Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke. Journal of Cerebral Blood Flow & Metabolism2007
14.        Dewaza et al., Potential of Bone Marrow Stromal Cells in Applications for Neuro- Degenerative, Neuro-Traumatic and Muscle Degenerative Diseases. Current Neuropharmacology 2005
15.        Bliss et al., Cell Transplantation Therapy for Stroke. Stroke 2007
16.        Wechsler, Stem cell transplantation for stroke.Cleveland Clinic Journal of Medicine2004
17.        Andreas et al., Cell replacement therapy for intracerebral hemorrhage. Neurosurg Focus2008
18.        Taguchi et al., Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. The Journal of Clinical Investigation 2004

Spinal Cord Injury
1.        Choong et al., Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro. Cytotherapy 2007
2.        Bang et al, Autologous Mesenchymal Stem Cell Transplantation in Stroke Patients. American Neurological Association 2005
3.        Deng et al., Implantation of BM mesenchymal stem cells into injured spinal cord elicits de Novo neurogenesis and functional recovery: evidence from a study in rhesus monkey. Cytotherapy 2006
4.        Shi et al., Intrathecal injection of bone marrow stromal cells attenuates neurologic injury after spinal cord ischemia. Ann Thorac Surg 2006
5.        Shi et al., Therapeutic Benefit of Intrathecal Injection of Marrow Stromal Cells on Ischemia-Injured Spinal Cord. Ann Thorac Surg 2007
6.        Kyung et al., Neurons Derived From Human Mesenchymal Stem Cells Show Synaptic Transmission and Can Be Induced to Produce the Neurotransmitter Substance P by Interleukin-1α. Stem Cells 2005
7.        Hafstetter et al., Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. PNAS 2002
8.        Liu et al., Axonal Sprouting into the Denervated Spinal Cord and Synaptic and Postsynaptic Protein Expression in the Spinal Cord after Transplantation of Bone Marrow Stromal Cell in Stroke Rats. Brain Res. Author manuscript 2008
9.        Schultz et al., Adult Stem Cell Application in Spinal Cord Injury. Current Drug Targets 2005
10.        Helm et al., Future uses of mesenchymal stem cells in spine surgery. Neurosurg Focus 2005

shenxiu2

"MSC can be found mainly in bone marrow which is widely acknowledged as the purer, richer and safer source of MSC. Other adult sources of MSC are umbilical cord blood, peripheral blood and fat. Researchers found that MSC are very rare in peripheral blood and umbilical cord blood and cannot be consistently obtained."
这儿说到间充质干细胞(Mesenchymal stem cell ),就是在心脏治疗(或软骨,肾脏等治疗)中所用的干细胞,在骨髓中最多,在脐带血中不多,因此需要抽取骨髓来培植.
有意思的是,在这个研究团队中(都是华裔),有一位专家是来自中国的.

f117a

shenxiu2 是Mayo医学中心？？:shutup:

shenxiu2

8# f117a
我的名字是猎户座腰带中间的那颗星。我的博客就叫做"我家在猎户座“。:lol
不，我不在Mayo‘s clinic。我在一家小医院做个小小麻醉医生而已。
高兴认识你。:handshake