Mesenchymal Stem Cells (MSCs) Are of Interest in the Clinic Because of their Immunomodulation Capabilities, Capacity to Act Upstream of Inflammation, and Ability to Sense Metabolic Environments. in Standard Physiologic Conditions, They Play a Role in Maintaining the Homeostasis of Tissues and Organs; However, there is Evidence that They Can Contribute to Some Autoimmune Diseases. Gaining a Deeper Understanding of the Factors that Transition MSCs from their Physiological Function to a Pathological Role in their Native Environment, and Elucidating Mechanisms that Reduce their Therapeutic Relevance in Regenerative Medicine, is Essential. We Conducted a Systematic Review and Meta-Analysis of Human MSCs in Preclinical Studies of Autoimmune Disease, evaluating 60 Studies that Included 845 Patient Samples and 571 Control Samples. MSCs from Any Tissue Source Were Included, and the Study Was Limited to Four Autoimmune Diseases: Multiple Sclerosis, Rheumatoid Arthritis, Systemic Sclerosis, and Lupus. We Developed a Novel Risk of Bias Tool to Determine Study Quality for in Vitro Studies. using the International Society for Cell & Gene Therapy's Criteria to Define an MSC, Most Studies Reported No Difference in Morphology, Adhesion, Cell Surface Markers, or Differentiation into Bone, Fat, or Cartilage When Comparing Control and Autoimmune MSCs. However, There Were Reported Differences in Proliferation. Additionally, 308 Biomolecules Were Differentially Expressed, and the Abilities to Migrate, Invade, and Form Capillaries Were Decreased. the Findings from This Study Could Help to Explain the Pathogenic Mechanisms of Autoimmune Disease and Potentially Lead to Improved MSC-Based Therapeutic Applications.