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Biomedical subjects

Thomas Ming Swi Chang

Publications and source records attributed to Thomas Ming Swi Chang.

At least 19 recordsLinked to original sources
PubMed2006

Blood substitutes based on nanobiotechnology.

Stimulated by concerns of potential infective agents in donated blood, commercial enterprises have attempted to develop blood substitutes since the 1900s. After several years of development, a few of the many leads are showing promise. In this article, nanobiotechnological approaches that are now in phase III clinical trials are reviewed, followed by a discussion of how important basic knowledge gained is being used to develop new generations of blood substitutes based on nanobiotechnology.

Animals↗
PubMed2006

Transdifferentiation of bioencapsulated bone marrow cells into hepatocyte-like cells in the 90% hepatectomized rat model.

Under specific conditions, bone marrow cells can transdifferentiate into a variety of cell types including hepatocytes. In this study, bioencapsulated bone marrow cells were transplanted intraperitoneally into 90% hepatectomized rats. We then followed the transdifferentiation of the bone marrow cells and the effect of this on liver regeneration in this liver failure model. Bone marrow cells isolated from Wistar rats were bioencapsulated using alginate-polylysine-alginate method. These bioencapsulated bone marrow cells were transplanted intraperitoneally into 90% hepatectomized Wistar rats. Blood chemistry, HGF, liver weight, and survival of the recipient rats were evaluated. Histology and immunocytochemistry were used to analyze the bioencapsulated cells before and 14 days after transplantation. Unlike free bone marrow cells, transplantation of bioencapsulated bone marrow cells improved the survival of 90% hepatectomized rats and improved the blood chemistry with an efficacy similar to that of bioencapsulated hepatocytes or free hepatocytes transplantation. Some bioencapsulated bone marrow cells expressed hepatocytes markers of cytokeratins 8, cytokeratins 18, albumin, and AFP after 2 weeks of transplantation. These results suggest that syngeneic bioencapsulated bone marrow cells can transdifferentiate into hepatocyte-like cells in the peritoneal cavity of 90% hepatectomized rats and increased the survival rates of these rats. In conclusion, these findings suggest the potential for a new alternative to hepatocyte transplantation for cellular therapy of acute liver failure.

Animals↗
PubMed2006

Coencapsulation of hepatocytes and bone marrow cells: in vitro and in vivo studies.

Bioencapsulation of cells is one of the many areas of artificial cells being extensively investigated by centers around the world. This includes the bioencapsulation of hepatocytes. A number of methods have been developed to maintain the specific function and phenotype of the bioencapsulated hepatocytes for in vitro and in vivo applications. These include supplementation of factors in the culture medium; use of appropriate substrates and the co-cultivation of hepatocytes with other type of cells, the so called "feeder cells". These feeder cells can be of liver origin or non-liver origin. We have recently studied the role of bone marrow cells in the maintenance of hepatocytes viability and phenotype by using the coculture of hepatocytes with bone marrow cells (nucleated cells including stem cells), and the coencapsulation of hepatocytes with bone marrow stem cells. This way, the hepatocytes viability and specific function can be maintained significantly longer. In vivo studies of both syngeneic and xenogeneic transplantation show that the hepatocytes viability can be maintained longer when coencapsulated with bone marrow cells. Transplantation of coencapsulated hepatocytes and bone marrow cells enhances the ability of the hepatocytes in correcting congenital hyperbilirubinmia in Gunn rats. Both in vitro and in vivo studies show that bone marrow cells can enhance the viability and phenotype maintenance of hepatocytes. Thus, bone marrow cells play an important role as a new type of feeder cells for bioencapsulated hepatocytes for the cellular therapy of liver diseases.

Alginates↗
PubMed2006

Polyhemoglobin with different percentage of tetrameric hemoglobin and effects on vasoactivity and electrocardiogram.

There has been considerable discussions on why some types of haemoglobin-based blood substitutes increase vasoactivity whereas a very few others do not. In this study, we prepare four different types of PolyHb each containing different percentage of tetrameric hemoglobin using glutaraldehyde crosslinking and characterized to ensure that they all have the same oxygen affinity. Thus the preparations are prepared from the same chemical method and have the same oxygen affinity. We infused these in the form of 1/6 volume toploading into anesthetized rats to simulate the use of blood substitutes in surgery. Mean arterial pressure (MAP) increased immediately after injection of PolyHb containing 38% or 78% of tetrameric hemoglobin. However, there was no significant increase in blood pressure with the injection of PolyHb containing 16% or 0.4% tetrameric hemoglobin. In electrocardiogram (ECG) study, we observe that high percentage (78%) of tetrameric hemoglobin causes marked changes in ECG immediately after infusion. Injection of PolyHb containing 16% or 38% of tetrameric hemoglobin resulted in minimal elevation of the ST segment. Infusion of PolyHb containing 0.4% of tetrameric hemoglobin did not result in any changes.

Animals↗
PubMed2006

Evolution of artificial cells using nanobiotechnology of hemoglobin based RBC blood substitute as an example.

The original artificial red blood cells have evolved into oxygen carriers in the form of polyhemoglobin and conjugated hemoglobin. Clinical conditions requiring only oxygen carriers are responding well to these types of oxygen carriers without the need for a complete artificial red blood cell. For those conditions requiring more than just oxygen carriers, new generations of polyhemoglobin containing antioxidant enzymes are being developed. Though a complete artificial red blood cell comparable to red blood cell is still a dream, development in lipid membrane artificial red blood cells and biodegradable polymeric nano artificial red blood cells are steps towards this possibility. The many years of neglect on basic research in the area of blood substitutes have resulted in the lack of important basic knowledge needed for the rapid development of blood substitutes suitable for clinical use. This is further hampered by the mistaken conception that blood substitute is a single entity. We need to look at blood substitutes as consisting of progressively more complicated entities, e.g. oxygen carriers, oxygen carriers with antioxidant activity, and complete red blood cell substitutes. Each of these entities is not applicable to all clinical conditions, but is suitable for specific applications.

Antioxidants↗
PubMed2005

Therapeutic applications of polymeric artificial cells.

Polymeric artificial cells have the potential to be used for a wide variety of therapeutic applications, such as the encapsulation of transplanted islet cells to treat diabetic patients. Recent advances in biotechnology, molecular biology, nanotechnology and polymer chemistry are now opening up further exciting possibilities in this field. However, it is also recognized that there are several key obstacles to overcome in bringing such approaches into routine clinical use. This review describes the historical development and principles behind polymeric artificial cells, the present state of the art in their therapeutic application, and the promises and challenges for the future.

Animals↗
PubMed2005

Transplantation of bioencapsulated bone marrow stem cells improves hepatic regeneration and survival of 90% hepatectomized rats: a preliminary report.

We transplanted bioencapsulated bone marrow stem cells intraperitoneally into 90% hepatectomized rats and found that this increases both the rates of hepatic regeneration and survival of the animals. Bone marrow cells isolated from Wistar rats were bioencapsulated using alginate-polylysine-alginate method. These bioencapsulated bone marrow cells were transplanted intraperitoneally into 90% hepatectomized syngeneic wistar rats. Control groups included 90% hepatectomized group receiving intraperitoneal injection of either empty microcapsules or free bone marrow cells. Unlike the control groups, transplantation of bioencapsulated bone marrow cells improved the survival of 90% hepatectomized rats, with an efficacy similar to that of bioencapsulated hepatocytes or free hepatocytes. These results suggest that syngeneic bioencapsulated bone marrow stem cells can increase the survival rates of 90% hepatectomized rats. We also discuss the potential for a new alternative to hepatocyte transplantation for cellular therapy of acute liver failure. In particular, bone marrow stem cells can be obtained from the same patient with no immunorejection, whereas in hepatocyte transplant, immunosuppressant will be needed to prevent immunorejection of the donor hepatocytes.

Alginates↗
PubMed2004

Effects of long-term oral administration of polymeric microcapsules containing tyrosinase on maintaining decreased systemic tyrosine levels in rats.

There is no effective treatment for melanoma, a fatal skin cancer occurring with increasing frequency. Dietary tyrosine restriction lowers systemic tyrosine and suppresses the growth of melanoma in mice, but this is not tolerated by human resulting in nausea, vomiting, and weight loss. We report here the successful use of oral polymeric microcapsules containing tyrosinase to lower the systemic tyrosine level in the rats. We found that microencapsulated tyrosinase incubated with intestinal content of rats selectively lowered the tyrosine level. We then studied the daily oral administration of microencapsulated tyrosinase in rats of one dose a day, two doses a day, and three doses a day over a period of up to 22 days. With three doses a day, the tyrosine levels in the test group decreased to 68.8% of the control group by day 4 and then decreased to 52.6% after this and remained at this level throughout the 22 days test period. This is the level shown earlier by other workers using dietary restriction of tyrosine to result in suppression of growth of melanoma. However, unlike dietary tyrosine restriction, oral tyrosinase microcapsules did not result in adverse effects nor significant differences in growth (weight gain) when compared to the control group. This approach can also be used for the lowering of systemic tyrosine in hypertyrosinemia, an inborn error of metabolism.

Administration, Oral↗
PubMed2004

History, challenges and perspectives of cell microencapsulation.

Cell microencapsulation continues to hold significant promise for biotechnology and medicine. The controlled, and continuous, delivery of therapeutic products to the host by immunoisolated cells is a potentially cost-effective method to treat a wide range of diseases. Although there are several issues that need to be addressed, including capsule manufacture, properties and performance, in the past few years, a stepwise analysis on the essential obstacles and limitations has brought the whole technology closer to a realistic proposal for clinical application. This paper summarizes the current situation in the cell encapsulation field and discusses the main events that have occurred along the way.

Cell Transplantation↗
PubMed2004

Artificial cell bioencapsulation in macro, micro, nano, and molecular dimensions: keynote lecture.

Artificial cells now ranges from macro-dimensions, to micron-dimensions, to nano-dimensions, and to molecular dimensions. Those in the macro-dimensions are suitable for use in the bioencapsulation of cells, tissues, microorganisms, and bioreactants. Those in the micron-dimensions are suitable for the bioencapsulation of enzymes, microorganisms, peptides, drugs, vaccine, and other materials. Those in the nano-dimension are being used for blood substitutes and carriers for enzymes, peptides, drugs, etc. Those in the molecular-dimensions are used as blood substitutes, crosslinked enzymes etc.

Animals↗
PubMed2004

Effects of combined oral administration and intravenous injection on maintaining decreased systemic tyrosine levels in rats.

Our previous studies have indicated that encapsulated tyrosinase and crosslinked hemoglobin with tyrosinase (polyhemoglobin-tyrosinase) decrease systemic tyrosine level significantly in rats. However, we need a few days of oral administration of encapsulated tyrosinase before the systemic tyrosine level starts to decrease. Although intravenous injection of polyhemoglobin tyrosinase can lower the systemic tyrosine to about 10% within an hour, the level increases towards normal after 24 h. We therefore investigate the effects of intravenous injection of polyhemoglobin-tyrosinase combined with oral administration of encapsulated tyrosinase on lowering the systemic tyrosine level. In addition, we further optimize this combined method for lowering systemic tyrosine in animal studies and have found out that two intravenous injections of polyhemoglobin-tyrosinase followed by three times a day oral administration of encapsulated tyrosinase could immediately lower the body tyrosine and maintain this low level as long as the oral administration is continued.

Administration, Oral↗
PubMed2004

Polyhemoglobin-tyrosinase, an oxygen carrier with murine B16F10 melanoma suppression properties: a preliminary report.

Melanoma now represents the fifth most common cancer in North America and it has increased dramatically in the past decade. One of the approaches shows that lowering of tyrosine level can inhibit the growth of melanoma in cell culture and in mice bearing B16BL6 melanoma. However, human cannot tolerate the tyrosine restricted diets for lowering tyrosine due to nausea, vomiting, and severe body weight loss. We therefore prepare a novel soluble polyhemoglobin-tyrosinase complex. Our studies show that this preparation can lower systemic tyrosine level in normal animals. This preparation also prevents the native tyrosinase from having adverse effects and from rapid removal after injection. In cell culture study, we find that this preparation inhibits the growth of murine B16F10 melanoma culture. Furthermore, in animal studies we observe that daily intravenous injection of this polyhemoglobin-tyrosinase preparation significantly delays the growth of B16F10 melanoma in mice, without causing adverse effects or changes in the growth of the treated animals.

Aldehydes↗
PubMed2004

In vitro and in vivo effects of polyhaemoglobin-tyrosinase on murine B16F10 melanoma.

Melanoma is an increasingly common fatal skin cancer. Many groups are carrying out research on potential treatments for melanoma. One of these approaches has shown that lowering tyrosine can inhibit the growth of melanoma in cell cultures and of B16BL6 melanoma in mice. However, humans cannot tolerate tyrosine-restricted diets for lowering tyrosine because of nausea, vomiting and weight loss. We report here our preparation and characterization of a novel soluble polyhaemoglobin-tyrosinase complex. This preparation prevents native tyrosinase from having adverse effects and from rapid removal after injection. The preparation inhibited murine B16F10 melanoma cell growth in culture and delayed its growth in a mice model. Intravenous injection of the preparation lowers the systemic tyrosine level without causing adverse effects such as vomiting and weight loss in mice. It is therefore possible that this complex could be useful in the treatment of human melanoma.

Animals↗
PubMed2004

Hemoglobin-based red blood cell substitutes.

Polyhemoglobin is already well into the final stages of clinical trials in humans with one approved for routine clinical use in South Africa. Conjugated hemoglobin is also in ongoing clinical trials. Meanwhile, recombinant Hb has been modified to modulate the effects of nitric oxide. Other systems contain antioxidant enzymes for those clinical applications that may have potential problems related to ischemia-reperfusion injuries. Other developments are based on hemoglobin-lipid vesicles and also the use of nanotechnology and biodegradable copolymers to prepare nanodimension artificial red blood cells containing hemoglobin and complex enzyme systems.

Animals↗
PubMed2004

Artificial cells for cell and organ replacements.

The artificial cell is a Canadian invention (Chang, Science, 1964). This principle is being actively investigated for use in cell and organ replacements. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion for use in the removal of drugs, and toxins and waste in uremia and liver failure. Encapsulated cells are being studied for the treatment of diabetes, liver failure, and kidney failure, and the use of encapsulated genetically-engineered cells is being investigated for gene therapy. Blood substitutes based on modified hemoglobin are already in Phase III clinical trials in patients, with as much as 20 units being infused into each patient during trauma surgery. Artificial cells containing enzymes are being developed for clinical trial in hereditary enzyme deficiency diseases and other diseases. The artificial cell is also being investigated for drug delivery and for other uses in biotechnology, chemical engineering, and medicine.

Artificial Organs↗
PubMed2003

Artificial cells for replacement of metabolic organ functions.

Artificial cells are being actively investigated for use in the replacement of cell and organ functions, especially related to metabolic functions. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion. Implantation of encapsulated cells are being studied for the treatment of diabetes, liver failure, kidney failure and the use of encapsulated genetically engineered cells for gene therapy. Blood substitutes based on modified hemoglobin are already in Phase III clinical trials in patients with as much as 20 units infused into each patient during trauma surgery. Artificial cells containing enzymes are being developed for clinical trial in hereditary enzyme deficiency diseases and other diseases. Artificial cell is also being investigated for drug delivery and for other uses in biotechnology, chemical engineering and medicine.

Artificial Organs↗
PubMed2002

Increased viability of transplanted hepatocytes when hepatocytes are co-encapsulated with bone marrow stem cells using a novel method.

This study is to investigate the viability of hepatocytes when transplanted into Wistar rats using co-encapsulated hepatocytes and bone marrow stem cells. Hepatocytes and bone marrow stem cells, isolated from Wistar rats, are co-encapsulated using either the standard single-step method or a novel two-step cell encapsulation method (www.artcell.mcgill.ca). After intraperitoneal transplantation into Wistar rats, the histology, fate of recovered microcapsules and viability of encapsulated hepatocytes are studied. When prepared using the standard method, there is excellent viability but only for up to 3 weeks. After this, there is extensive fibrous coating and severe fibrous adhesion and no microcapsules can be recovered. On the other hand, using the new two-step encapsulation method, the viability of the encapsulated hepatocytes can be followed for more than 4 months after transplantation. Even up to 4 months, there is significantly less host reaction when using the two-step encapsulation method and 50% of the microcapsules can be recovered. Co-encapsulated with bone marrow stem cells resulted in further increase in viability of the hepatocytes when followed up to 4 months after transplantation. This new approach may improve the potential feasibility of using co-encapsulation of hepatocytes and bone marrow stem cells in bio-artificial liver support for the treatment of liver failure, especially for acute liver failure.

Animals↗