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Article ; Online: Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1.

Leung, Adrian On Wah / Poon, Andrew Chung Hin / Wang, Xue / Feng, Chen / Chen, Peikai / Zheng, Zhengfan / To, Michael KaiTsun / Chan, Wilson Cheuk Wing / Cheung, Martin / Chan, Danny

Nature communications

2024 Volume 15, Issue 1, Page(s) 2229

Abstract: Apoptosis occurs during development when a separation of tissues is needed. Synovial joint formation is initiated at the presumptive site (interzone) within a cartilage anlagen, with changes in cellular differentiation leading to cavitation and tissue ... ...

Abstract	Apoptosis occurs during development when a separation of tissues is needed. Synovial joint formation is initiated at the presumptive site (interzone) within a cartilage anlagen, with changes in cellular differentiation leading to cavitation and tissue separation. Apoptosis has been detected in phalangeal joints during development, but its role and regulation have not been defined. Here, we use a mouse model of brachydactyly type A1 (BDA1) with an Ihh
MeSH term(s)	Mice ; Animals ; Hedgehog Proteins/metabolism ; Brachydactyly/genetics ; Brachydactyly/metabolism ; Joints/metabolism ; Apoptosis
Chemical Substances	Hedgehog Proteins
Language	English
Publishing date	2024-03-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45053-0
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Article ; Online: Regulation and Role of Transcription Factors in Osteogenesis.

Chan, Wilson Cheuk Wing / Tan, Zhijia / To, Michael Kai Tsun / Chan, Danny

International journal of molecular sciences

2021 Volume 22, Issue 11

Abstract: Bone is a dynamic tissue constantly responding to environmental changes such as nutritional and mechanical stress. Bone homeostasis in adult life is maintained through bone remodeling, a controlled and balanced process between bone-resorbing osteoclasts ... ...

Abstract	Bone is a dynamic tissue constantly responding to environmental changes such as nutritional and mechanical stress. Bone homeostasis in adult life is maintained through bone remodeling, a controlled and balanced process between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoblasts secrete matrix, with some being buried within the newly formed bone, and differentiate to osteocytes. During embryogenesis, bones are formed through intramembraneous or endochondral ossification. The former involves a direct differentiation of mesenchymal progenitor to osteoblasts, and the latter is through a cartilage template that is subsequently converted to bone. Advances in lineage tracing, cell sorting, and single-cell transcriptome studies have enabled new discoveries of gene regulation, and new populations of skeletal stem cells in multiple niches, including the cartilage growth plate, chondro-osseous junction, bone, and bone marrow, in embryonic development and postnatal life. Osteoblast differentiation is regulated by a master transcription factor RUNX2 and other factors such as OSX/SP7 and ATF4. Developmental and environmental cues affect the transcriptional activities of osteoblasts from lineage commitment to differentiation at multiple levels, fine-tuned with the involvement of co-factors, microRNAs, epigenetics, systemic factors, circadian rhythm, and the microenvironments. In this review, we will discuss these topics in relation to transcriptional controls in osteogenesis.
MeSH term(s)	Animals ; Bone and Bones/physiology ; Cell Differentiation/genetics ; Gene Expression Regulation/genetics ; Humans ; Osteogenesis/genetics ; Transcription Factors/genetics ; Transcription, Genetic/genetics
Chemical Substances	Transcription Factors
Language	English
Publishing date	2021-05-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22115445
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Article: Extracellular Matrix and Cellular Plasticity in Musculoskeletal Development.

Ma, Sophia Ka Yan / Chan, Andy Shing Fung / Rubab, Aqsa / Chan, Wilson Cheuk Wing / Chan, Danny

Frontiers in cell and developmental biology

2020 Volume 8, Page(s) 781

Abstract: Cellular plasticity refers to the ability of cell fates to be reprogrammed given the proper signals, allowing for dedifferentiation or transdifferentiation into different cell fates. ...

Abstract	Cellular plasticity refers to the ability of cell fates to be reprogrammed given the proper signals, allowing for dedifferentiation or transdifferentiation into different cell fates.
Language	English
Publishing date	2020-08-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2020.00781
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Article ; Online: Haploidentical Transplant Achieves Long-Term Remission in Relapsed Refractory Leukemia With Fludarabine-Induced Neurotoxicity Complication.

Chan, Wilson Y K / Yeung, W L / Shelia, Wong S N / Tso, Winnie W Y / Cheung, Claudia / Kan, Elaine Y L / Lee, Pamela P W / Cheuk, Daniel K L / Ha, Shau Yin / Leung, Wing

Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation

2023 Volume 21, Issue 3, Page(s) 279–285

Abstract: Hematopoietic stem cell transplant is potentially curative for relapsed/refractory leukemia. However, neurotoxicity is common and has been reported in 11% to 59% of children following hematopoietic stem cell transplant. Most pediatric studies of the ... ...

Abstract	Hematopoietic stem cell transplant is potentially curative for relapsed/refractory leukemia. However, neurotoxicity is common and has been reported in 11% to 59% of children following hematopoietic stem cell transplant. Most pediatric studies of the neurological effects of hematopoietic stem cell transplant have focused on acute neurotoxicity. Limited information is available for long-term neurotoxicity, particularly those cases that are severe and permanent and caused by conditioning chemotherapy. Here, we report 2 cases of relapsed acute lymphoblastic leukemia that achieved long-term remission by haploidentical hematopoietic stem cell transplant but remained complicated with severe and persistent fludarabine-induced neurotoxicity.
MeSH term(s)	Humans ; Child ; Hematopoietic Stem Cell Transplantation/adverse effects ; Vidarabine/adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Transplants ; Transplantation Conditioning
Chemical Substances	fludarabine (P2K93U8740) ; Vidarabine (FA2DM6879K)
Language	English
Publishing date	2023-03-29
Publishing country	Turkey
Document type	Case Reports ; Journal Article
ZDB-ID	2396778-X
ISSN	2146-8427 ; 1304-0855
ISSN (online)	2146-8427
ISSN	1304-0855
DOI	10.6002/ect.2022.0383
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Article ; Online: Blinatumomab with donor lymphocyte infusions post haploidentical hematopoietic stem cell transplantation as salvage therapy for relapsed refractory acute lymphoblastic leukemia post chimeric antigen receptor T-cell therapy.

Chan, Wilson Y K / Lee, Pamela P W / Cheuk, Daniel K L / Yeung, Eva W M / Wong, Kenneth C W / Li, C K / Chan, Godfrey C F / Leung, Wing

Pediatric blood & cancer

2022 Volume 70, Issue 1, Page(s) e29852

MeSH term(s)	Humans ; Salvage Therapy ; Receptors, Chimeric Antigen ; Antibodies, Bispecific/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Lymphocytes
Chemical Substances	blinatumomab (4FR53SIF3A) ; Receptors, Chimeric Antigen ; Antibodies, Bispecific
Language	English
Publishing date	2022-06-23
Publishing country	United States
Document type	Letter
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.29852
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Article ; Online: Regulation and Role of Transcription Factors in Osteogenesis

Wilson Cheuk Wing Chan / Zhijia Tan / Michael Kai Tsun To / Danny Chan

International Journal of Molecular Sciences, Vol 22, Iss 5445, p

2021 Volume 5445

Abstract	Bone is a dynamic tissue constantly responding to environmental changes such as nutritional and mechanical stress. Bone homeostasis in adult life is maintained through bone remodeling, a controlled and balanced process between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoblasts secrete matrix, with some being buried within the newly formed bone, and differentiate to osteocytes. During embryogenesis, bones are formed through intramembraneous or endochondral ossification. The former involves a direct differentiation of mesenchymal progenitor to osteoblasts, and the latter is through a cartilage template that is subsequently converted to bone. Advances in lineage tracing, cell sorting, and single-cell transcriptome studies have enabled new discoveries of gene regulation, and new populations of skeletal stem cells in multiple niches, including the cartilage growth plate, chondro-osseous junction, bone, and bone marrow, in embryonic development and postnatal life. Osteoblast differentiation is regulated by a master transcription factor RUNX2 and other factors such as OSX/SP7 and ATF4. Developmental and environmental cues affect the transcriptional activities of osteoblasts from lineage commitment to differentiation at multiple levels, fine-tuned with the involvement of co-factors, microRNAs, epigenetics, systemic factors, circadian rhythm, and the microenvironments. In this review, we will discuss these topics in relation to transcriptional controls in osteogenesis.
Keywords	bone ; osteogenesis ; transcription factor ; osteoblast ; osteoblast differentiation ; epigenetics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Outcomes of allogeneic transplantation for hemoglobin Bart's hydrops fetalis syndrome in Hong Kong.

Chan, Wilson Y K / Lee, Pamela P W / Lee, Vincent / Chan, Godfrey C F / Leung, Wing / Ha, S Y / Cheuk, Daniel K L

Pediatric transplantation

2021 Volume 25, Issue 6, Page(s) e14037

Abstract: Background: Hemoglobin Bart's hydrops fetalis syndrome (BHFS) was once considered a fatal condition universally. Medical advances over the past three decades have resulted in increasing numbers of BHFS survivors. This retrospective review summarized ... ...

Abstract	Background: Hemoglobin Bart's hydrops fetalis syndrome (BHFS) was once considered a fatal condition universally. Medical advances over the past three decades have resulted in increasing numbers of BHFS survivors. This retrospective review summarized local territory-wide experience and outcomes of BHFS patients who received allogeneic hematopoietic stem cell transplantation (HSCT) in Hong Kong. Methods: All BHFS patients who underwent allogeneic HSCT in Hong Kong, either in one of the two former pediatric transplant centers (Queen Mary Hospital and Prince of Wales Hospital) on or before 2019 or in the single territory-wide pediatric transplant center (Hong Kong Children's Hospital) since 2019, from January 1, 1996, till December 31, 2020, were included. Basic demographic data, perinatal history, transplant details, long-term outcomes, and morbidities were reviewed. Results: Total five allogeneic HSCT were performed in two males and three females at a median age of 22 months, which include one 8/8 matched-sibling bone marrow transplant, one 5/6 matched-sibling cord blood transplant with HLA-DR antigenic mismatch, two 12/12 matched-unrelated peripheral blood stem cell transplant (PBSCT), and one haploidentical PBSCT with TCRαβ/CD45RA depletion from maternal donor. Neutrophil and platelet engrafted (>20 × 10 Conclusion: To conclude, local data demonstrated favorable outcome of allogeneic HSCT for BHFS patients, but sample number is small. Non-directive approach in counseling and international collaboration is recommended.
MeSH term(s)	Female ; Hematopoietic Stem Cell Transplantation ; Hemoglobins, Abnormal ; Hong Kong ; Humans ; Hydrops Fetalis/therapy ; Infant ; Male ; Retrospective Studies ; Transplantation, Homologous
Chemical Substances	Hemoglobins, Abnormal ; hemoglobin Bart's (9056-09-1)
Language	English
Publishing date	2021-05-18
Publishing country	Denmark
Document type	Journal Article ; Multicenter Study
ZDB-ID	1390284-2
ISSN	1399-3046 ; 1397-3142
ISSN (online)	1399-3046
ISSN	1397-3142
DOI	10.1111/petr.14037
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Zs.A 4947: Show issues

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Article ; Online: Successful haploidentical hematopoietic stem cell transplantation (HSCT) and durable engraftment by repeated donor lymphocyte infusions for a Chinese patient with transfusion-dependent hemoglobin (Hb) Hammersmith and massive splenomegaly.

Chan, Wilson Y K / Chan, Nelson C N / So, Jason C C / Lee, Pamela P W / Cheuk, Daniel K L / Ha, S Y / Chan, Godfrey C F / Leung, Wing

Pediatric transplantation

2022 Volume 26, Issue 5, Page(s) e14278

Abstract: Background: Hemoglobin (Hb) Hammersmith is a rare form of unstable β-chain hemoglobinopathy causing hemolytic anemia. This rare event led to a more serious transfusion-dependent phenotype in a patient. It was successfully cured by haploidentical ... ...

Abstract	Background: Hemoglobin (Hb) Hammersmith is a rare form of unstable β-chain hemoglobinopathy causing hemolytic anemia. This rare event led to a more serious transfusion-dependent phenotype in a patient. It was successfully cured by haploidentical hematopoietic stem cell transplantation (HSCT). Methods and results: A 9-year-old mainland Chinese male with a history of neonatal unconjugated hyperbilirubinemia was diagnosed to have hemoglobin (Hb) Hammersmith. He required regular blood transfusion but was unable to be transfused to desired parameters for 8 years prior to transplant due to social and geographical reasons. He subsequently developed marrow hyperplasia and progressive splenomegaly (down to umbilicus level), suggestive of extramedullary hematopoiesis. Eventually, the family came to Hong Kong and complied to a more intensive transfusion regimen and preconditioning chemotherapy 3 months prior to transplant. He underwent haploidentical HSCT using paternal TCRαβ/CD45RA-depleted graft but suffered from graft rejection, despite splenic irradiation for massive splenomegaly. It was successfully salvaged with second HSCT with unmanipulated graft from the same donor with additional serotherapy and donor lymphocyte infusions. Conclusion: Allogenic haploidentical HSCT for hemoglobin Hammersmith is feasible but adequate immunosuppression during conditioning is crucial. Precise adoptive cell therapy can promote durable engraftment.
MeSH term(s)	Asians ; Child ; Haploidy ; Hematopoietic Stem Cell Transplantation ; Hemoglobins, Abnormal ; Humans ; Living Donors ; Lymphocyte Transfusion ; Lymphocytes ; Male ; Splenomegaly/etiology ; Splenomegaly/therapy ; Transfusion Reaction
Chemical Substances	Hemoglobins, Abnormal ; hemoglobin Hammersmith (37359-23-2)
Language	English
Publishing date	2022-04-09
Publishing country	Denmark
Document type	Case Reports ; Journal Article
ZDB-ID	1390284-2
ISSN	1399-3046 ; 1397-3142
ISSN (online)	1399-3046
ISSN	1397-3142
DOI	10.1111/petr.14278
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Article ; Online: Epidemiology and outcomes of pediatric transplant-associated thrombotic microangiopathy in Hong Kong.

Chan, Wilson Yau Ki / Ma, Alison Lap Tak / Chan, Eugene Yu Hin / Kan, Amanda Nim Chi / Ng, Wai Fu / Lee, Pamela Pui Wah / Cheuk, Daniel Ka Leung / Chiang, Alan Kwok Shing / Leung, Wing / Chan, Godfrey Chi Fung

Pediatric transplantation

2022 Volume 26, Issue 7, Page(s) e14366

Abstract: Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is an under-recognized yet potentially devastating complication of hematopoietic stem cell transplantation (HSCT) which had increased awareness in recent years. This report summarizes ...

Abstract	Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is an under-recognized yet potentially devastating complication of hematopoietic stem cell transplantation (HSCT) which had increased awareness in recent years. This report summarizes the demographics and outcomes of pediatric TA-TMA in Hong Kong. Methods: All patients aged below 18 years who underwent HSCT in the Hong Kong Children's Hospital and were diagnosed to have TA-TMA during the 2-year period from April 1, 2019 to March 31, 2021 were included. Results: A total of 73 transplants (51 allogeneic and 22 autologous) in 63 patients had been performed. Six patients (four males and two females) developed TA-TMA at a median duration of 2.5 months post-HSCT. The incidence rate was 9.52%. Of the six TA-TMA patients, five underwent allogenic one underwent autologous HSCT, respectively. Three of them were histologically proven. All four patients with cyclosporine had stopped the drug once TA-TMA was suspected. Median six doses of eculizumab were administered to five out of six patients. Three patients died (two due to fungal infection and one due to acute-on-chronic renal failure) within 3 months upon diagnosis of TA-TMA. Among three survivors, two stabilized with mild stage 2 chronic kidney disease (CKD) while the other suffered from stage 5 end-stage CKD requiring lifelong dialysis. Conclusion: In conclusion, recognition and diagnosis of TA-TMA are challenging. Early recognition and prompt administration of complement blockage with eculizumab may be beneficial in selected cases. Further prospective research studies are recommended to improve the management and outcomes of TA-TMA.
MeSH term(s)	Aged ; Child ; Cyclosporins ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hong Kong/epidemiology ; Humans ; Male ; Renal Insufficiency, Chronic/etiology ; Thrombotic Microangiopathies/diagnosis ; Thrombotic Microangiopathies/epidemiology ; Thrombotic Microangiopathies/etiology
Chemical Substances	Cyclosporins
Language	English
Publishing date	2022-07-21
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1390284-2
ISSN	1399-3046 ; 1397-3142
ISSN (online)	1399-3046
ISSN	1397-3142
DOI	10.1111/petr.14366
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Article ; Online: Extracellular Matrix and Cellular Plasticity in Musculoskeletal Development

Sophia Ka Yan Ma / Andy Shing Fung Chan / Aqsa Rubab / Wilson Cheuk Wing Chan / Danny Chan

Frontiers in Cell and Developmental Biology, Vol

2020 Volume 8

Abstract: Cellular plasticity refers to the ability of cell fates to be reprogrammed given the proper signals, allowing for dedifferentiation or transdifferentiation into different cell fates. In vitro, this can be induced through direct activation of gene ... ...

Abstract	Cellular plasticity refers to the ability of cell fates to be reprogrammed given the proper signals, allowing for dedifferentiation or transdifferentiation into different cell fates. In vitro, this can be induced through direct activation of gene expression, however this process does not naturally occur in vivo. Instead, the microenvironment consisting of the extracellular matrix (ECM) and signaling factors, directs the signals presented to cells. Often the ECM is involved in regulating both biochemical and mechanical signals. In stem cell populations, this niche is necessary for maintenance and proper function of the stem cell pool. However, recent studies have demonstrated that differentiated or lineage restricted cells can exit their current state and transform into another state under different situations during development and regeneration. This may be achieved through (1) cells responding to a changing niche; (2) cells migrating and encountering a new niche; and (3) formation of a transitional niche followed by restoration of the homeostatic niche to sequentially guide cells along the regenerative process. This review focuses on examples in musculoskeletal biology, with the concept of ECM regulating cells and stem cells in development and regeneration, extending beyond the conventional concept of small population of progenitor cells, but under the right circumstances even “lineage-restricted” or differentiated cells can be reprogrammed to enter into a different fate.
Keywords	extracellular matrix ; plasticity ; development ; limb regeneration ; chondrocyte ; hypertrophic chondrocyte ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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