Hepatocyte transplantation is an alternative to liver transplantation that aims to restore hepatic function without replacing the entire organ. It involves transplanting isolated hepatocytes from donor livers into patients with liver-based metabolic disorders or acute liver failure. While hepatocyte transplantation is less invasive than liver transplantation and allows multiple patients to be treated from a single donor, challenges remain such as ensuring an adequate number of engrafted cells and long-term correction of the metabolic abnormality without immunosuppression. Current research is focused on overcoming these hurdles to expand the clinical application of hepatocyte transplantation.
Allogeneic hematopoietic stem cell transplantation (allo HSCT) from an HLA-matched related donor provides the most potent anti-leukemic effect of any post-remission therapy in AML, as demonstrated by the lowest rates of relapse.
Graft vs leukemia plays and important role here.
Provides the best chance of long-term survival
Allogeneic hematopoietic stem cell transplantation (allo HSCT) from an HLA-matched related donor provides the most potent anti-leukemic effect of any post-remission therapy in AML, as demonstrated by the lowest rates of relapse.
Graft vs leukemia plays and important role here.
Provides the best chance of long-term survival
The collection and processing of hematopoieticakshaya tomar
BASICS OF HSC COLLECTION AND PROCESSING INCLUDING ALL THE THREE SOURCES, A BRIEF ABOUT STEM CELL MOBILIZATION, STEM CELL SELECTION CRYOPRESERVATION AND DMSO
Living donor liver transplantation (LDLT) is performed all over the world today. The shortage of cadaveric grafts makes it the only option for many end stage cirrhotics in many countries. Donor hepatectomy is a complicated operations and this has raised concerns about the safety of this operation. However, today donor hepatectomy is a safe operation with a low incidence of complications.
What process is used to obtain cells from bone marrow and normal peripheral blood?
What is the best cell counting and viability method for primary cells?
AllCells, your primary cells research partner, and Nexcelom Bioscience, your cell counting experts, have joined together in an exclusive collaboration to host a free webinar to help educate researchers and present data from their own experiences.
Selection and maintenance of a cadaver donor for liver transplantationApollo Hospitals
The need for the cadaver organ for liver transplant is increasing. Extended criteria/marginal donors can increase the donor pool significantly as ideal donors are very few. The combination of multiple marginal factors seems to be additive on graft injury. Although the organs from marginal donors may not be optimal, they are a viable alternative to dying while waiting for transplantation. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described. It is inferred that older donors, mild to moderate steatosis, hypernatremia (preferably after correction), high ianotropic requirement, bacteremia, etc. are acceptable. Selected patients with low-grade malignancy may be accepted. Donors with positive viral serologies where transmission to the recipient is possible should be used only if the recipient is already infected with the same agent or the recipient has a critical need. The importance of liver biopsy and the goals of donor maintenance are also described. It is also concluded that the patients with high model for end-stage liver disease (MELD) score (>20) benefit the most with the marginal organs.
Cell Storage Best Practices: Techniques to Ensure Greater Research Resultsallcells
Featuring: Cryopreservation Specialist, Michael George
This webinar will introduce cell storage equipment and techniques in order to provide the most up-to-date trends in research today. There will be special emphasis on human primary cell storage, cryopreservation, and transportation.
Topics to be covered in the webinar:
• Background on life science storage methods
• Advantages/disadvantages of storage equipment
• What not to do (common mistakes/misconceptions)
• Interview with James Lee, Associate Director of Production, AllCells
• Q&A
The collection and processing of hematopoieticakshaya tomar
BASICS OF HSC COLLECTION AND PROCESSING INCLUDING ALL THE THREE SOURCES, A BRIEF ABOUT STEM CELL MOBILIZATION, STEM CELL SELECTION CRYOPRESERVATION AND DMSO
Living donor liver transplantation (LDLT) is performed all over the world today. The shortage of cadaveric grafts makes it the only option for many end stage cirrhotics in many countries. Donor hepatectomy is a complicated operations and this has raised concerns about the safety of this operation. However, today donor hepatectomy is a safe operation with a low incidence of complications.
What process is used to obtain cells from bone marrow and normal peripheral blood?
What is the best cell counting and viability method for primary cells?
AllCells, your primary cells research partner, and Nexcelom Bioscience, your cell counting experts, have joined together in an exclusive collaboration to host a free webinar to help educate researchers and present data from their own experiences.
Selection and maintenance of a cadaver donor for liver transplantationApollo Hospitals
The need for the cadaver organ for liver transplant is increasing. Extended criteria/marginal donors can increase the donor pool significantly as ideal donors are very few. The combination of multiple marginal factors seems to be additive on graft injury. Although the organs from marginal donors may not be optimal, they are a viable alternative to dying while waiting for transplantation. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described. It is inferred that older donors, mild to moderate steatosis, hypernatremia (preferably after correction), high ianotropic requirement, bacteremia, etc. are acceptable. Selected patients with low-grade malignancy may be accepted. Donors with positive viral serologies where transmission to the recipient is possible should be used only if the recipient is already infected with the same agent or the recipient has a critical need. The importance of liver biopsy and the goals of donor maintenance are also described. It is also concluded that the patients with high model for end-stage liver disease (MELD) score (>20) benefit the most with the marginal organs.
Cell Storage Best Practices: Techniques to Ensure Greater Research Resultsallcells
Featuring: Cryopreservation Specialist, Michael George
This webinar will introduce cell storage equipment and techniques in order to provide the most up-to-date trends in research today. There will be special emphasis on human primary cell storage, cryopreservation, and transportation.
Topics to be covered in the webinar:
• Background on life science storage methods
• Advantages/disadvantages of storage equipment
• What not to do (common mistakes/misconceptions)
• Interview with James Lee, Associate Director of Production, AllCells
• Q&A
Liver transplant (LT) is becoming the need of the hour and often the last ray of hope for many of our cirrhotic patients. The dearth of deceased donors, acceptance of living-related donors, better operative skills, and post transplant outcomes have played an important role is making LT accessable to more and more needy people. However, for best outcome it is important to stick to the established criteria laid down for listing a patient for LT for both best outcomes and better distribution of donor livers.
Cirrhosis results from different mechanisms of liver injury that lead to necroinflammation and fibrogenesis; Patients
with liver cirrhosis often require liver transplantation but it is affected by many problems, including relative operative
damage, high costs, lack of donors, and risk of rejection. Currently studies are shown the Stem cell therapy has the
potential to provide a valuable adjunct to the management of disease, Stem cell should be the natural candidates to
provide a renewable source of cells for transplantation.
The main mechanism of stem cell therapy is that stem cell capacity to differentiate into any of the hundreds of distinct
cell types that comprise the human body. In addition to their potential in therapeutics can be used to study the earliest
stages of human development and disease modeling using human cells.
Keywords: Cell Therapy; Liver Cirrhosis; Stem Cell; Transplantation. limitlessly, and often play the principal role in
liver regeneration
Pediatric Liver Transplant (LT) is now an established procedure for End Stage Liver Disease (ESLD) with biliary atresia being the commonest indication. Intensive pre-transplant evaluation, nutritional buildup and immunization are the fundamental pre-requisites of a successful LT. With improvement in surgical micro-anastomotic techniques and superior immunosuppressive regimens the success rate of pediatric LT is in excess of 90%. Most of the transplants in our country however are Living related, due to which a fairly large number of children expire awaiting a donor liver. There should be a concerted effort to evolve the cadaveric donation program, so that majority of the children are benefitted.
Will someone from the family gift your child their liver?Jia Maheshwari
Never say never - never lose hope. You never know when a liver donor will be found and be a blessing for your family member suffering from end stage liver disease. But a lot of caution and care is required to guard against increasing instances of post surgery complications such as ones related to the biliary tract.
The application of nanotechnology, microfluidics, bioreactors with kidney cells, and miniaturized sorbent systems to regenerate dialysate makes clinical reality seem closer than ever before. Finally, stem cells hold much promise, But more far realistic. In summary, nephrology is at an exciting crossroad with the application of innovative and novel technologies to RRT that hold considerable promise for the near future. Bioartificial Kidney as an ideal form of RRT would mimic the functions of natural kidneys and be affordable to the patient
INTRODUCTION
HISTORY
NEED OF SYNCHRONIZATION
SYNCHRONOUS CULTURES CAN BE OBTAINED IN SEVERAL WAYS:
Physical fractionation .
Chemical appro ach
CENTRIFUGAL ELUTRIATION
Inhibition of DNA synthesis
Nutritional deprivation
SYNCHRONIZATION AT LOW TEMPERATURE
CELLULAR TOTIPOTENCY
SOME HIGHLIGHTS OF CELL SYNCHRONIZATION
REFERENCES
The field of organ transplantation has made remarkable progress in a short period of time.
Transplantation has evolved to become the treatment of choice for end-stage organ failure resulting from almost any of a wide variety of causes .
Human Stem Cells- Introduction
Types of HSC transplants
Indications
Sources of stem cells
Collection and mobilization
Types of Mobilizing agents
Processing
Cryopreservation and storage
PBSC Transplant
Quality control
Complications
Primary sclerosing cholangitis (PSC) is a chronic, idiopathic, cholestatic liver disease characterized histologically by peribiliary inflammation and fibrosis.
It can lead to end stage cirrhosis and is a recognized risk factor for hepatobiliary cancers
A fibroscan is a test used to help measure the amount of scarring (fibrotic tissue) in the liver. It’s essentially a specialized ultrasound specifically for the liver
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdf
Hepatocyte transplant.dr quiyum
1. Will hepatocyte transplantation replace
liver transplantation ? Future aspect
DR MD AB QUIYUM
PHASE B
HEPATOBILIARY ,PANCREATIC & LIVER TRANSPLANT SURGERY
2. Introduction
Liver transplantation is the accepted treatment for patients with acute
liver failure and liver-based metabolic disorders.
However, donor organ shortage and lifelong need for immunosuppression
are the main limitations to liver transplantation.
In addition, loss of the native liver as a target organ for future gene
therapy for metabolic disorders limits the futuristic treatment options,
resulting in the need for alternative therapeutic strategies.
A potential alternative to liver transplantation is allogeneic hepatocyte
transplantation
3. Aim
The aim of hepatocyte transplantation in patients
presenting metabolic disorders is to restore hepatic
functions without replacing the entire organ.
4. Indication
2 major disease ..
1. liver-based metabolic disorders that do not lead to cirrhosis.
Crigler-Najjar syndrome, in which there is a defect in the enzyme that
conjugates bilirubin
urea cycle disorders, in which there is abnormal processing of amino
acids, leading to elevated ammonia levels;
and phenylketonuria, in which phenylalanine is not processed
2. acute liver failure.
In general, candidate conditions for hepatocyte transplantation are those in
which the architecture of the liver is intact.
5. The number of cells necessary for
correcting a deficit is unknown
For example, Crigler-Najjar syndrome, 12% of the liver mass is necessary
LIVER ..2.8% of the TBW , 1.5 kg/ADULT.
The minimum liver mass.. survival .. 10–30% of the total organ or 200–600 g.
Considering 120 million human hepatocytes/gram of tissue, a minimum of 2.5–7.5
billion cells would be required for a clinical therapeutic treatment
Nevertheless, major challenges for the wide clinical application of hepatocyte therapy include
availability, metabolic integrity, and sufficient amount of cells for transplantation.
Transplanted cells are generally no longer observed after 6–9 months and it is not clear if
this is due to rejection, apoptosis, or other causes.
109 cells are required for cell therapy
6. Source
unviable organs for transplantation would become sources of viable
hepatocytes for transplantation.
Each year, a large number of cadaverous donor livers for transplantation are
rejected.
The reasons include high-grade steatosis, nonviral cirrhosis, and death due to
heart failure
7. . Human hepatocytes are isolated from
(i) whole donor livers unsuitable/rejected for OLT, mostly because of
severe steatosis, prolonged ischemia time, older, or non-heart-beating
donors, or
(ii) from liver segments, mainly I and IV, which are available for cell
isolation after split liver transplantation.
3. fetal and neonatal livers are being explored as a potential cell
source as they are currently not considered for OLT and may allow
the isolation of very high-quality cells .
4. Explanted livers from patients with liver-based metabolic disorders
have also been considered as a potential source of cells,so-called
“domino” liver transplantation
8.
9. procedure
a standardized three-step collagenase perfusion technique
First, major hepatic vessels are cannulated and perfused with Hank’s buffered
salt solution (HBSS) containing EGTA, which is able to chelate calcium ions, thus
disrupting the desmosomes, calcium-dependent cell-to-cell adhesions.
Second, the liver is flushed with plain HBSS to remove any residue of EGTA.
Third, the tissue is perfused with a calcium-dependent collagenase solution to
digest the extracellular matrix.
After breaking of the liver capsule, the released liver cells are filtered and
centrifuged at low speed to separate hepatocytes from nonparenchymal cells.
10. Hepatocytes can be used fresh for transplantation or cryopreserved.
cryopreserving 106–107 cells/ml in the University of Wisconsin organ
preservation solution
Cryopreserved hepatocytes are then stored at –140 °C until required for HT.
Most centers consider a dose of 2 × 108 cells per kg of body weight as the
upper safe limit for hepatocyte transplantation
11. lack of anchorage for the transplanted cells and
host immune response.. viability. encapsulation
of hepatocytes in alginate microbeads ..
prolonging survival.
hepatocyte-like cells (HLCs) , iPSC-derived HLCs,
safety concern for clinical applications is their
tumorigenic potential, which needs to be solved
before these cells can be used safely in humans
12.
13. Hepatocytes …sinusoidal vessels ….transient occlusions in the
periportal vascular areas .. followed by restoration of normal blood
flow by vascular permeabilization,
which allows transplanted cells to reach the liver parenchyma
Hepatocytes remaining in the portal vessels are cleared by
macrophages within 24 h.
The number of cells injected is limited by portal pressure, which
should be monitored throughout by Doppler ultrasound, and should
not exceed 12 mm Hg to avoid the risk of portal hypertension (
14. Is it reversible ?
1. significant infection
2. an immune suppression–related complication,
3. a patient decides to undergo a hepatocyte transplantation, his or her
access to a donor organ and ability to receive an organ transplant is not
affected.
IF If a patient undergoes hepatocyte transplantation and the procedure does
not adequately correct the liver abnormality, then liver transplantation is
performed as originally planned.
If a donated organ becomes available during the observation period following
hepatocyte transplantation and the disease has not been corrected liver
transplantation be performed.
15. In Cirrhosis ???
the native liver is structurally abnormal.
Donor hepatocytes are not able to get into the liver because of a thickening of
the extracellular matrix.
Placing hepatocytes in extrahepatic locations, such as the spleen or in a
lymph node, may be effective, but this approach has not been tested
clinically.
In the latest approach … a decellularized liver from an animal, such as a pig, is
repopulated with viable hepatocytes and other types of liver cells, which can
then be used as a bioartificial liver that could potentially be engrafted into the
patient.
16. challenges
1. supply of an adequate number of cells into the liver .
2.Isolated hepatocytes .. viable for 48 hours after isolation … transplanted
within this time frame.
3. capacity of the portal vein …. Portal hypertension .. varices and gastrointestinal
bleeding.
4. Thrombosis of the portal circulation .. liver dysfunction.
5.shunting..translocate to the lungs…cardiovascular instability or pulmonary
insufficiency
6. too late diagnosis
7. engraftment
8. difficult to identify transplanted cells by biopsy… difficult.. Predict rejection.
9. not interested .. experimental intervention, preferring instead to wait for an
organ transplant.
17. Potential solution
1.cells from multiple donors
2 to infuse them over a long period of time.
3. low-dose irradiation .. short-term loss of the endothelial cells ..enter the liver.
selectively grow ..replaced by donor cells.
4.. stem cells will be harvested from the peripheral blood after stimulation of
bone marrow. with more frequent doses of G-CSF followed by autologous
transfusion of harvested stem cells,
18.
19.
20. Advantage
1.Chance of spontaneous patient recovery,
2. increasing patient survival rate while awaiting donation
21. Disadvantage
1. immunosuppressive regimens include
induction with steroids and calcineurin
inhibitors (tacrolimus or cyclosporine) .
Some centers have also included therapy
with anti-interleukine-2 receptor
antibodies (basiliximab) 1.
2. ultimately need OLT
22. Difference
With liver transplantation, the entire organ is replaced.
If there is acute or chronic rejection that compromises the liver and cannot
be controlled, then the patient may require retransplantation.
With hepatocyte transplantation, only a small fraction of liver cells—
hepatocytes, the metabolic engine of the liver—are replaced, leaving intact
all of the other types of cells within the liver, including endothelial cells,
stellate cells, Kupffer cells, and fibroblasts.
With this approach to transplantation, between 5% and 15% of the host’s liver
is replaced with transplanted hepatocytes.
is difficult to identify transplanted cells by biopsy, which is routinely
performed in organ transplant recipients, so it is difficult to know definitively
whether the donor cells are being rejected until it is too late to intervene.
23. hepatocyte transplantation has several
advantages over OLT
: (i) it is less invasive and less expensive not involving a complex surgery;
(ii) it can be performed repeatedly if required;
(iii) cryopreserved cells isolated from donor livers are available immediately
when needed;
(iv) native liver remains in place serving as a backup in case of cell graft failure
and allowing potential regeneration in patients with acute liver failure (ALF), as
well as representing a possible target for future gene therapy in patients with
liver-based metabolic disorders; and
(v) because this procedure only requires a fraction of the cells isolated from a
donor organ, multiple patients can be treated from one donor tissue, thus saving
other organs for patients who do require OLT.
24. Current Status
The experience worldwide has been similar from center to center.
down to less than half of their initial values
partial correction is not adequate because the patients remain at risk for
severe brain injury.
In almost all cases, the patients have ultimately received an organ transplant.
25. Future aspect
The last two decades have seen a considerable development of hepatocyte
transplantation, with demonstration of short-term efficacy and safety.
However, some hurdles still need to be overcome to widen hepatocyte
transplantation clinical applications,
mainly regarding isolation of high-quality cells from marginal donor liver,
improvement of cell engraftment, and long-lasting effects, as well as optimal
immunosuppression regimen identification.
26. Take home message
With improvements in optimizing delivery technique and assessing
proper recipients of livers, monitoring graft function, as well as
recognizing and treating graft rejection, HTx may be able to be used
more widely in metabolic liver disease and potentially delay necessity
of OLT.