Review
Pharmacology & Pharmacy
Cornelia Lee-Thedieck, Peter Schertl, Gerd Klein
Summary: This review provides a comprehensive overview of the extracellular matrix (ECM) in hematopoietic stem cell (HSC) niches and highlights its importance in regulating cellular function and niche structure. The role of different classes of ECM molecules and their interactions with cells are discussed, along with the significance of matrix remodeling and biophysics in HSC niche function. The review also examines the application of current knowledge of ECM in artificial HSC niches for HSC expansion, targeted differentiation, and drug testing.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Engineering, Biomedical
Yinbo Xiao, ChanelleA. S. McGuinness, W. Sebastian Doherty-Boyd, Manuel Salmeron-Sanchez, Hannah Donnelly, Matthew J. Dalby
Summary: Hematopoietic stem cells play a fundamental role in the generation of blood and immune cells. Although the signaling mechanisms in their bone marrow niche microenvironment have been increasingly understood, the ability to recreate these mechanisms in vitro for clinical purposes is still lacking. Recent studies have used engineering techniques to establish ex vivo bone marrow niche models, showing promising potential for research and clinical applications.
Review
Engineering, Biomedical
Chandralekha Chatterjee, Peter Schertl, Miriam Frommer, Anita Ludwig-Husemann, Anna Mohra, Nadine Dilger, Toufik Naolou, Sophia Meermeyer, Timna Claire Bergmann, Alejandro Alonso Calleja, Cornelia Lee-Thedieck
Summary: Artificial niches play a crucial role in regenerative medicine research, providing insights into the biophysical and biochemical processes of hematopoietic stem cells, as well as facilitating HSCs expansion and targeted differentiation. Due to the lack of natural microenvironment, biomaterials are essential in recreating niche environments, offering promising applications in various fields.
ACTA BIOMATERIALIA
(2021)
Review
Biochemistry & Molecular Biology
Nicole Pui-Yu Ho, Hitoshi Takizawa
Summary: This article summarizes the current understanding of how hematopoietic stem cell functions are maintained, damaged, or exhausted during acute, prolonged, and pathological inflammatory conditions. It also highlights the impact of inflammation-altered hematopoietic stem cell niche on escalating the insults on hematopoietic stem cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Anri Koyanagi, Iichiroh Onishi, Karin Muraoka, Ikue Sato, Shingo Sato, Tsuyoshi Kimura, Akio Kishida, Kouhei Yamamoto, Masanobu Kitagawa, Morito Kurata
Summary: Hematopoiesis is maintained by the interaction of hematopoietic stem cells and bone marrow mesenchymal stem cells in bone marrow microenvironments. Certain genetic mutations in the mesenchymal stem cells can lead to hematopoietic neoplasms. This study used a specific gene mutation in human mesenchymal stem cells and a bone scaffold to create an in vivo bone marrow microenvironment model, providing insights into these interactions and disease onset.
BIOENGINEERING-BASEL
(2022)
Article
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: Clinical evidence suggests a relationship between blood and bone, but the underlying mechanism is not fully understood. A study using beta-thalassemia as a model found that increased fibroblast growth factor 23 (FGF23) levels in patients and mice with beta-thalassemia were induced by erythropoietin via ERK1/2 and STAT5 pathways. Inhibiting FGF23 signaling with carboxyl-terminal FGF23 peptide rescued bone defects and restored hematopoietic stem cell function in mice with beta-thalassemia. FGF23 may serve as a molecular link connecting anemia, bone, and the hematopoietic stem cell niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Summary: This study demonstrates the overproduction of fibroblast growth factor 23 (FGF23) in patients and mice with beta-thalassemia, and shows that inhibition of FGF23 signaling is a safe and effective therapeutic strategy to rescue bone defects and restore hematopoietic stem cell function. FGF23 may serve as a molecular link connecting anemia, bone, and the HSC niche.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Chemistry, Medicinal
Annamaria Aprile, Silvia Sighinolfi, Laura Raggi, Giuliana Ferrari
Summary: Research in the last decade has shown multiple alterations of the BM niche in beta-thalassemia and sickle cell disease, emphasizing the importance of understanding the interaction between HSC biology and the BM microenvironment in improving clinical outcomes of transplantation.
Article
Pharmacology & Pharmacy
Chin-Chean Wong, Shi-Da Sheu, Pei-Chun Chung, Yi-Yen Yeh, Chih-Hwa Chen, Yen-Wei Chang, Tzong-Fu Kuo
Summary: This study investigated the therapeutic efficacy of direct intra-articular injection of bone-marrow-derived stem/stromal cells (BMSCs) and the role of hyaluronic acid (HA) in facilitating rabbit articular cartilage repair. Results showed that HA treatment could promote CD44 expression in BMSCs, while the combined BMSC and HA injection demonstrated better healing outcomes compared to BMSC or HA treatment alone in terms of gross grading and histological scores. The study highlights the potential of using a combination of HA and BMSCs as a convenient and effective formulation to improve stem-cell-based therapies for cartilage repair.
Article
Multidisciplinary Sciences
Kai Dai, Qinghao Zhang, Shunshu Deng, Yuanman Yu, Fuwei Zhu, Shuang Zhang, YuanZhong Pan, Dandan Long, Jing Wang, Changsheng Liu
Summary: Constructing in vivo osteo-organoids by implanting bone morphogenetic protein-2-loaded scaffolds into the internal muscle pocket near the femur of mice supports the growth and subsequent harvest of therapeutically useful cells, and these cells demonstrate therapeutic potentials in cell therapies such as mitigating chronic liver fibrosis and reconstituting impaired immune organs.
Article
Multidisciplinary Sciences
Hyun-Ji Park, Jessica R. Hoffman, Milton E. Brown, Sruti Bheri, Olga Brazhkina, Young Hoon Son, Michael E. Davis
Summary: Small extracellular vesicles (sEVs) play a critical role in cardiac cell therapy by delivering molecular cargo and mediating cellular signaling. Knocking down miR-192-5p and miR-432-5p in cardiac c-kit+ cell-derived sEVs enhances their therapeutic capabilities and improves cardiac function, reducing fibrosis and necrotic inflammatory responses. This study suggests that targeting deleterious miRNAs in sEVs could be a promising therapeutic strategy for chronic myocardial infarction.
Article
Biochemical Research Methods
Christa Haase, Karin Gustafsson, Shenglin Mei, Shu-Chi Yeh, Dmitry Richter, Jelena Milosevic, Raphael Turcotte, Peter Kharchenko, David B. Sykes, David T. Scadden, Charles P. Lin
Summary: Image-seq is a technology that allows single-cell transcriptional data to be obtained from cells isolated from specific spatial locations under image guidance, preserving the spatial information of the cells. It can be used with in situ and in vivo imaging to document the temporal and dynamic history of the cells being analyzed. This technology combines spatial information with highly sensitive RNA sequencing, providing valuable insights into cellular organization and function.
Article
Cell Biology
Bo Li, Jingya Li, Bingzhi Li, Takehito Ouchi, Longjiang Li, Yu Li, Zhihe Zhao
Summary: Craniofacial bones provide support and protection for the brain, with stem cells and their niches playing a key role in bone turnover. However, comprehensive studies of the cranial stem cell niches and age-related changes are lacking. In this study, single-cell RNA sequencing was used to analyze the transcriptomic profiles and cellular compositions of cranial stem cell niches during aging. The results revealed alterations in the bone marrow microenvironment influenced by inflammaging, identified senescent mesenchymal cell subclusters and age-related immune cell subclusters, and analyzed differentially expressed genes and cell-cell communications, providing insights into cranial bone biology and potential therapeutic targets for antiaging and regenerative medicine.
Article
Engineering, Biomedical
Michael R. Nelson, Delta Ghoshal, Joscelyn C. Mejias, David Frey Rubio, Emily Keith, Krishnendu Roy
Summary: The study presents a unique microfluidic hBM-on-a-chip that accurately mimics the human bone marrow microenvironment, providing new opportunities for research and intervention in bone marrow diseases. The complex structure of the chip increases experimental efficiency and reproducibility, while offering insights into the dynamics of hematopoietic stem cells.
Article
Oncology
Eman Khatib-Massalha, Simon Mendez-Ferrer
Summary: This article summarizes the diversity in ontogeny, functions, and cell-cell interactions of megakaryocytes (Mks). Mks are responsible for platelet production and also play a role in HSC maintenance and immune response. Dysfunction of the bone marrow microenvironment and mutated Mks can contribute to the development of various hematologic malignancies, including MPNs and fibrosis. Understanding the interactions between Mks, HSCs, and immune cells has potential clinical implications for stem cell transplantation and therapies for hematologic malignancies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Engineering, Biomedical
Andrew N. Rosenbaum, Alfredo L. Clavell, John M. Stulak, Atta Behfar
Summary: There is a lack of data on the invasive assessment of afterload and its impact on cardiac output in patients on LVAD therapy. Despite no direct association between mean aortic pressure (MAP) and cardiac index (CI), varying MAP levels led to different cardiac output responses to speed increments. Patients with elevated MAP were found to benefit from nitrate therapy, demonstrating improved biventricular filling pressures and increased cardiac index. High afterload in LVAD patients is common, but can be improved with nitrates, highlighting the importance of further research on the effects of high afterload and chronic vasodilator therapy in this patient population.
Article
Engineering, Biomedical
Andrew N. Rosenbaum, John M. Stulak, Alfredo L. Clavell, Atta Behfar
Summary: This study evaluated the prognostic significance of hemodynamic indices in LVAD patients and found that LVEDP is a central prognostic marker in this population.
Article
Engineering, Biomedical
Bradley Ternus, Atta Behfar, John Schirger, Gregory Barsness, Mackram Eleid, Parag Patel, John Stulak, Jacob Jentzer
Summary: This study aimed to evaluate the clinical outcomes of hemodynamic optimization using IABP in high-risk heart failure patients before LVAD implantation. The results showed that patients treated with IABP before LVAD implantation had better reductions in pulmonary artery pressures without an increase in postoperative complications.
Article
Cardiac & Cardiovascular Systems
Alexander J. Ryu, Vinayak Kumar, Barry A. Borlaug, Armando Manduca, Chaitanya K. Rao, Raymond J. Gibbons, Samuel J. Asirvatham, Bernard J. Gersh, Krishnaswamy Chandrasekaran, Philip A. Araoz, Jae K. Oh, Alexander C. Egbe, Atta Behfar, Nandan S. Anavekar
Summary: The study investigated the ratio of myocardial volume in systole to myocardial volume in diastole (MVs/MVd) to differentiate between normal hearts and various cardiomyopathies with normal ejection fractions.
Results showed significant differences in MVs/MVd ratio between pathological subgroups and normal subjects, suggesting its potential as a novel and easily-captured metric for assessing ventricular function.
The study concluded that MVs/MVd ratio can effectively distinguish normal ventricular function from different cardiomyopathies, indicating its clinical utility in assessing heart disease.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Andrew N. Rosenbaum, Bradley W. Ternus, Siddharth Pahwa, John M. Stulak, Alfredo L. Clavell, Sarah D. Schettle, Atta Behfar, Jacob C. Jentzer
Summary: In patients undergoing left ventricular assist device implantation, right ventricular stroke work index, right heart catheterization, cardiopulmonary bypass time, and ultrafiltration are strongly associated with incident INT-LD and decreased 1-year survival. Optimization of these factors may reduce the risk of liver dysfunction but further validation is needed.
ANNALS OF THORACIC SURGERY
(2021)
Article
Engineering, Biomedical
Andrew N. Rosenbaum, C. Charles Jain, Ilya Y. Shadrin, Stephanie C. El Hajj, Abdallah El Sabbagh, Atta Behfar
Summary: In patients with advanced heart failure, the use of percutaneous axillary intra-aortic balloon pump for temporary mechanical circulator support is feasible and associated with an acceptable complication rate as a bridge to definitive therapy, facilitating ambulation and improving outcomes.
Article
Cardiac & Cardiovascular Systems
Vinayak Kumar, Alexander J. Ryu, Armando Manduca, Chaitanya Rao, Raymond J. Gibbons, Bernard J. Gersh, Krishnaswamy Chandrasekaran, Samuel J. Asirvatham, Philip A. Araoz, Jae K. Oh, Alexander C. Egbe, Atta Behfar, Barry A. Borlaug, Nandan S. Anavekar
Summary: This study found that healthy myocardium is compressible, while myocardium in patients with heart failure with reduced ejection fraction is incompressible. The ratio MVs/MVd may need further investigation in different populations to understand its variations.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2021)
Article
Orthopedics
Guidong Shi, Yicun Wang, Zhanwen Wang, Andrew R. Thoreson, Daniel S. Jacobson, Peter C. Amadio, Atta Behfar, Steven L. Moran, Chunfeng Zhao
Summary: The study showed that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells, and formation of type III collagen.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2021)
Article
Cell & Tissue Engineering
Mark Li, Satsuki Yamada, Ao Shi, Raman Deep Singh, Tyler J. Rolland, Ryounghoon Jeon, Natalia Lopez, Lukas Shelerud, Andre Terzic, Atta Behfar
Summary: By introducing early cardiogenic genes, engineered cardiac repair competent stem cells with antioxidant, vasculogenic, and immunomodulatory traits have been successfully developed. These stem cells have important application value in treating heart diseases such as ischemic heart failure.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Richard C. Daly, Andrew N. Rosenbaum, Joseph A. Dearani, Alfredo L. Clavell, Naveen L. Pereira, Barry A. Boilson, Robert P. Frantz, Atta Behfar, Shannon M. Dunlay, Richard J. Rodeheffer, John A. Schirger, Timucin Taner, Manish J. Gandhi, Julie K. Heimbach, Charles B. Rosen, Brooks S. Edwards, Sudhir S. Kushwaha
Summary: This study demonstrates the successful transplantation using a heart-after-liver transplantation protocol, which provides profound immunologic protection and prevents adverse immunological outcomes in highly sensitized patients requiring combined heart-liver transplantation. The results show near-elimination of donor specific antibodies and minimal rejection episodes, leading to favorable long-term patient and graft outcomes.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Review
Cell & Tissue Engineering
Satsuki Yamada, Atta Behfar, Andre Terzic
Summary: Regenerative medicine aims to provide more care options for patients in need through technological innovation, helping them to get cured. Through responsible and regulated translation, regenerative medical technology is applied to the treatment of serious diseases and disabilities. By advancing the design, manufacture, and effectiveness of regenerative solutions, the goal is to democratize health benefits for all.
REGENERATIVE MEDICINE
(2021)
Article
Obstetrics & Gynecology
Cassandra K. Kisby, Ilya Y. Shadrin, Lillian T. Peng, Paul G. Stalboerger, Emanuel C. Trabuco, Atta Behfar, John A. Occhino
Summary: The study compared vaginal wound healing in a porcine mesh exposure model after exosome injection, looking at single vs. multiple dose regimens and acute vs. subacute exposure. Results showed that redosing with exosomes led to significantly higher epithelial proliferation and regenerated capillary density, with a trend towards thicker epithelium. Subacute exposure demonstrated similar regeneration to acute exposure despite a delayed injection timeline.
FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
(2021)
Editorial Material
Medicine, General & Internal
Michael S. Sabbah, Andrew N. Rosenbaum, Atta Behfar
MAYO CLINIC PROCEEDINGS
(2021)
Article
Cell & Tissue Engineering
D. Kent Arrell, Ruben J. Crespo-Diaz, Satsuki Yamada, Ryounghoon Jeon, Armin Garmany, Sungjo Park, Jeffrey P. Adolf, Christopher Livia, Matthew L. Hillestad, Jozef Bartunek, Atta Behfar, Andre Terzic
Summary: Stem cell paracrine activity, specifically secreted proteins by cardiopoietic cells, play a key role in cardiac repair. Through systems analytics and RNA sequencing, miR-146 was identified as a regulator upstream of the decoded secretome. The therapeutic impact of cardiopoietic cell therapy on infarcted hearts is influenced by the inherent vasculogenic properties and smooth muscle differentiation of the secreted proteins.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Ao Shi, Jialun Li, Xinyuan Qiu, Michael Sabbah, Soulmaz Boroumand, Tony Chieh-Ting Huang, Chunfeng Zhao, Andre Terzic, Atta Behfar, Steven L. Moran
Summary: This study developed a clinical-grade platelet exosome product (PEP) combined with injectable surgical fibrin sealant (TISSEEL) to promote chronic wound healing and skin regeneration. The PEP showed promising results in stimulating cellular activities and enhancing wound healing capacity.
