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Exogenous Matrix-supported Topical Application of Mesenchymal Stem Cells to Solid Organs

Summary
Stem cell is characterized by its their ability to self-renew and also transformed to various special functioning cells in the body in appropriate conditions. Human mesenchymal stem cells (MSCs) have attracted huge scientific interest as a therapy for various organ dysfunction, due to either degeneration or insults. To deliver the MSCs to the diseased organ, they are usually delivered by intravenous infusion in most animal experiments and clinical trials. This conventional route of MSCs administration is appealing because by selective cannulation of blood vessels supplying the target organ, large amount of cells can be transplanted by infusion to the organ. However, actually most of the infused cells do not stay in the target organ, and just follow the circulation and eventually trapped in other organs. Therefore the therapeutic potential of MSCs is compromised. Moreover, there are concerns about the retention of large amount of MSCs in other normal somatic organs which may have the potential risk of tumour formation. Finally, Intra-arterial administration of MSCs may cause arterial embolism or occlusion, and further affect the function of the diseased organ. Direct injection of MSCs through Hamilton syringe into target organs offers another way to deliver cells into the target organs. But it is an invasive procedure and poses certain risk of bleeding. In order not to causing excessive tissue damage, the injection volume and the cell quantity has to be limited, and hence the amount of MSCs delivered is limited. Furthermonre, before injection, the MSCs suspension has to be gently triurated through decreasing gauge needles in order to avoid cell clumps. This repeated triturations through the small needles will inevitably causing unavoidable cell damage which will adversely affects the cell viability I numbers and subsequent results. We have developed a novel approach of delivering MSCs to solid organs, in which MSCs ~e applied directly on ~ surface of the target organs. An ex,ogenous matrix is also used to support the MSC inoculation and proliferation. These topically applied MSCs will then migrate to the site of injury within the organ due to the chemotactic factors prodcued from the microenvironment and then further differentiated into the cells for tissue repair I regenerate. We have tested tested this novel approach in various injury models in rodents. The preliminary results were promising and this topical application has shown to provide an effective delivery for MSCs. As transplanted MSCs are directly applied to the target organs, the concerns of loss of MSCs and retention of MSCs by other normal somatic organs or tissues is minimized. Also, as the transplantation procedure is minimally invasive, multiple administrations of MSCs is feasible to patients. Therefore, the development of topical application of MSCs in this study will generate a significant impact on stem cell therapy because the therapeutic potential will be greatly enhanced.
Supplementary Information
Inventor: CHEN, Ying | DONG, Qi | HE, Ming-liang | KONG, Xiang-fu
Priority Number: CN102140473B
IPC Current: C12N001512 | A61K00317088 | A61K003817 | A61K004800 | A61P003500 | C07K001447 | C12N000115 | C12N000119 | C12N000121 | C12N000510 | C12N001563
Assignee Applicant: The Chinese University of Hong Kong
Title: Anti-tumor nucleic acid and polypeptide and application thereof
Usefulness: Anti-tumor nucleic acid and polypeptide and application thereof
Summary: The nucleic acid molecule, polypeptide, or vector is useful for preparing a medicament for treating tumor selected from liver cancer, gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, sarcoma, leukocythemia, ovarian cancer, carcinoma of the ureter, carcinoma of urinary bladder, prostatic cancer, lymphoma, multiple myeloma, pancreatic cancer, renal carcinoma, internal secretion gland cancer, skin cancer, melanoma, hemangioma and brain or CNS cancer (all claimed).
Novelty: New anti-tumor nucleic acid, useful for treating tumor comprising a defined nucleotide sequence of 249 bp
Industry
Disease Diagnostic/Treatment
Sub Category
Cancer/Tumor
Application No.
10/MED/373
Others
Inventor(s): Professor LAI Bo San Paul, Department of Surgery Patent Status: US Patent Pending Licensing Status: Available for licensing

Country/Region
Hong Kong

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