Leisheng Zhang

By Leisheng Zhang and Zhihai Han

Hydrogels are splendid biomaterials and play a critical role in multiple applications for disease management via offering a microenvironment for drug metabolism and exerting the bonding effect attribute to the preferable physical and chemical properties. State-of-the-art renewal has indicated the combination of hydrogels with mesenchymal stem/stromal cells (MSCs), which are heterogeneous populations with unique hematopoietic-supporting and immunoregulatory properties. For decades, we and other investigators have demonstrated the promising prospects of MSCs in regenerative medicine, and in particular, for the administration of recurrent and refractory disease. Very recently, we took advantage of the hydrogel/MSC composite for the applications in osteoarthritis, burn wounds, and refractory wounds associated with diabetic foot as well. Strikingly, the composite showed superiority in continuous improvement of the biological functions of the injured areas over hydrogels or MSCs, respectively. Collectively, hydrogel-based biomaterials are of importance for disease treatment and the accompanied regenerative medicine. Therefore, in this chapter, we will summarize the latest updates of hydrogel/MSCs composite in tissue engineering and put forward the direction of hotspot issues in the future including hydrogel/MSC and hydrogel/MSC-exosome in preclinical and clinical studies.

Part of the book: Hydrogels

By Leisheng Zhang, Zhihai Han, Zhongchao Han and Hui Cai

Osteoarthritis (OA), a principal and challenging disorder of articular cartilage, has been regarded as the most frequent and prevalent chronic disease of degenerative joints, which is caused by multiple factors including aging, trauma, overweight, joint deformity and congenital abnormality, together with the increase in life expectancy. In spite of considerable improvements that have been obtained by conducting multidisciplinary therapies such as surgical procedures and anti-inflammatory drugs, the pathogenesis and efficacy of OA with functional losses and degeneration are still elusively complicated for ascertainment. Mesenchymal stem/stromal cells (MSCs), also termed as multipotent mesenchymal progenitor/precursor cells, skeletal stem cells, or medicinal signaling cells, are heterogeneous cell populations with hematopoietic-supporting and immunomodulatory properties, together with multilineage differentiation property. For decades, investigators have illuminated the application of the advantaged and promising sources with/without remarkable biomaterials for the treatment of recurrent and refractory disorders including OA. In this chapter, we mainly concentrate on the current progress of MSC-based cytotherapy in both preclinical study and clinical practice as well as the promising prospective and critical challenges in the field, which will conformably benefit the administration of OA in future.

Part of the book: Arthroplasty

By Baoquan Song and Leisheng Zhang

Ferroptosis is a newly defined programmed cell death (PCD) process with the hallmark of the accumulation of iron-dependent lipid peroxidation, which is more immunogenic over apoptosis. Ferroptosis shows great potential as a therapeutic target against acute kidney injury (AKI), cancers, cardiovascular diseases, neurodegenerative diseases, and hepatic diseases. Accumulating evidence has highlighted that ferroptosis plays an unneglectable role in regulating the development and progression of multiple pathologies of leukemia including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Herein, we focus on the state-of-the-art renewal in the relationship of ferroptosis with leukemia. Meanwhile, this chapter further highlights the iron, lipid and amino acid metabolism, as well as ferroptosis-based molecular mechanisms. Collectively, we summarize the contribution of ferroptosis to the pathogenesis of leukemia and discuss ferroptosis as a novel therapeutic target for different types of leukemia.

Part of the book: Cell Death and Disease

By Leisheng Zhang, Xiaoming Feng, Zhihai Han and Zhongchao Han

Natural killer (NK) cells are advantaged immune cells and play a pivotal role in both innate and adaptive immune responses. To date, autogenous and allogenic NK cells have been generated from a variety of origins, including perinatal blood (e.g., umbilical cord blood and placental blood), peripheral blood, and even stem cells (hematopoietic stem cells and pluripotent stem cells). NK cells function mainly via antibody-dependent cell-mediated cytotoxicity (ADCC), direct cytolytic effect, and paracrine effects (e.g., IFN-γ, GM-CSF, granzyme, and perforin). Distinguishing from the adaptive immunizing cells (e.g., T and B lymphocytes), NK cells, and chimeric antigen receptor-transduced NK (CAR-NK), cell-based cytotherapy is adequate to fulfill the biofunction of eliminating pathogenic infection, combating hematological malignancies and metastatic solid tumors, and delaying aging. In this chapter, we mainly focus on the state-of-the-art renewal of NK cell-based cytotherapy for cancer immunosurveillance and immunotherapy from the view of high-efficient in vitro preparation (e.g., candidate cell sources and ex vivo cultivation) and preclinical and clinical investigation. Furthermore, we also figure out the promising prospects and the concomitant challenges of NK cell-based remedies for cancer management in future, which will collectively benefit the development of NK cell-based cancer immunotherapy in future.

Part of the book: Natural Killer Cells

By Shixun Ma, Li Li, Jintang Yin, Xiaohu Wang, Chongya Yang, Leisheng Zhang, Tiankang Guo and Hui Cai

Gastric cancer is one of the common malignant tumors in the gastrointestinal tract, and the treatment of gastric cancer includes the main ways such as radical resection, adjuvant chemotherapy, palliative care, and drug therapy; however, patients often have defects such as high recurrence rate, high treatment burden, and serious side effects, which impose a heavy burden on the economic and social construction and patients’ families. In recent years, novel gastric cancer treatment methods featuring tumor immunotherapy have provided new treatment strategies to improve the above-mentioned defects and increase the cure rate of patients. Natural killer cells (NK cells) are key components of the body’s intrinsic immune response and can participate in both the intrinsic and adaptive immune responses, exercising the functions of tumor killing, removing pathogenic microorganisms or abnormal cells and enhancing immunity, and thus have broad prospects for new drug development and clinical treatment. This article reviews the biological properties and functions of NK cells and their interrelationship with gastric cancer treatment, and provides a reference for clinical research.

Part of the book: Natural Killer Cells